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PROTOCOL
I
PROTOCOL fllfllIJltllq1mlaquom
uuJinHWU1tJfll1 ii JIll 390(l)l3946Q~rjjj 26 f11Jfl~flWj 2539
L ACUTE LEUKEMIA
11 Acute lloll-Iympboblastic
leukemia (ANLL)
A) Previously untreated case ICvtosmLe arabinoside 2
100 mglm
tnt) Consolidation therapy Cytosine arabinoside
2 mgm
100 mgm 2
2 60 mgm
Maintenance therapy
Regimen A (llfUVU Consolidation lhorapy)
Regimen B (vtnp arabinoside
6-Thiogaunine 2
40 mgm
2
Pbase 2
single dose 1000 mg)
2 75 mgm
2 60 mgm
2 10 mgm
15 rog)
irradiation 240y
Consolidation 2
Pbase 1 14 mgro
single dose 2 mg)
2 25 mgro
2 10 mgm
2
Pbase 2 650 mgm
2 75 mgm
2
Thioguanine mgm
2
Maintenance 6middotMercaptopurine mgm
2 Methotrexate mgm
J
3
2J Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Protocol for treatment
Arm-I COP without maintenance
Vincristine
2 750 mgm
2 14 mgm
2 100 mgm
Arm-ll COP with IFN maintenance
as Arm-I regimen)
maintenance IInterferon alfa-2A Mu
Arm-ill I-COP with IFN maintenance
Vincristine
Prednisolone
j ITnterferrn a1fa-2A
2 750 mgm
2 14 mgm
2 100 mgm
6Mu
maintenance maintenance as Arm-II regimen
B) Intermediate grade (lG)
and Hlgb grade (HG)
NHL
Arm-I CHOP-I
Adriamycin mgm
2 Vincristine 14 mgm
2 Prednisolone 60 mgm
alfa-2B Mu
Maintenance alfa-2B Mu
2
middot 4
Arm-n CHOP with COP maintenance
2 Cyclophosphamide 50 mgm
2 50 mgm
2 Vincristine 14 mgm
2
Maintenance Cyclophosphamide
2 Vincristine 14 mghn
2
mgm
60 mgm
Arm-ill CHOP without maintenance
Induction regimen as Arm-IT
C) Other types of NHL Cyclophosphamide
2 Vincristine 14 mgm
2 60 mgm
2 mgm
D) Failure Progrion Relapse or Stable disease
Option 1 ENAP regimen
2 100 mgm
2 10 mgm
2 I~rtnltn arabinoside 100 mgm
2 Prednisolone 100 mghn
Option 2 MINE regimen -----------------~~--------------------~ Mesna mg
2 133 mgm
2 8 mgm
2 Etoposide mgm
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
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J ( ~ ~ -- -I SL lt ~ ---
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YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
I
PROTOCOL fllfllIJltllq1mlaquom
uuJinHWU1tJfll1 ii JIll 390(l)l3946Q~rjjj 26 f11Jfl~flWj 2539
L ACUTE LEUKEMIA
11 Acute lloll-Iympboblastic
leukemia (ANLL)
A) Previously untreated case ICvtosmLe arabinoside 2
100 mglm
tnt) Consolidation therapy Cytosine arabinoside
2 mgm
100 mgm 2
2 60 mgm
Maintenance therapy
Regimen A (llfUVU Consolidation lhorapy)
Regimen B (vtnp arabinoside
6-Thiogaunine 2
40 mgm
2
Pbase 2
single dose 1000 mg)
2 75 mgm
2 60 mgm
2 10 mgm
15 rog)
irradiation 240y
Consolidation 2
Pbase 1 14 mgro
single dose 2 mg)
2 25 mgro
2 10 mgm
2
Pbase 2 650 mgm
2 75 mgm
2
Thioguanine mgm
2
Maintenance 6middotMercaptopurine mgm
2 Methotrexate mgm
J
3
2J Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Protocol for treatment
Arm-I COP without maintenance
Vincristine
2 750 mgm
2 14 mgm
2 100 mgm
Arm-ll COP with IFN maintenance
as Arm-I regimen)
maintenance IInterferon alfa-2A Mu
Arm-ill I-COP with IFN maintenance
Vincristine
Prednisolone
j ITnterferrn a1fa-2A
2 750 mgm
2 14 mgm
2 100 mgm
6Mu
maintenance maintenance as Arm-II regimen
B) Intermediate grade (lG)
and Hlgb grade (HG)
NHL
Arm-I CHOP-I
Adriamycin mgm
2 Vincristine 14 mgm
2 Prednisolone 60 mgm
alfa-2B Mu
Maintenance alfa-2B Mu
2
middot 4
Arm-n CHOP with COP maintenance
2 Cyclophosphamide 50 mgm
2 50 mgm
2 Vincristine 14 mgm
2
Maintenance Cyclophosphamide
2 Vincristine 14 mghn
2
mgm
60 mgm
Arm-ill CHOP without maintenance
Induction regimen as Arm-IT
C) Other types of NHL Cyclophosphamide
2 Vincristine 14 mgm
2 60 mgm
2 mgm
D) Failure Progrion Relapse or Stable disease
Option 1 ENAP regimen
2 100 mgm
2 10 mgm
2 I~rtnltn arabinoside 100 mgm
2 Prednisolone 100 mghn
Option 2 MINE regimen -----------------~~--------------------~ Mesna mg
2 133 mgm
2 8 mgm
2 Etoposide mgm
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
c-a Ch - 16( t1 fl v)u -ri ~ N ~ ~ cp )~gt1 L ~r M J ~ f ~ ~lLgt1
~ lmiddot5L1 bull
) l ) C
bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull~middot~bullbullbull ~ bullbullI~~~~~~0~J~bullbullbullbullbullmiddotbullbullmiddotbullbullmiddotbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull ~(Jt~
u u ~ uuu uu
Llt+-~
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
2
Pbase 2
single dose 1000 mg)
2 75 mgm
2 60 mgm
2 10 mgm
15 rog)
irradiation 240y
Consolidation 2
Pbase 1 14 mgro
single dose 2 mg)
2 25 mgro
2 10 mgm
2
Pbase 2 650 mgm
2 75 mgm
2
Thioguanine mgm
2
Maintenance 6middotMercaptopurine mgm
2 Methotrexate mgm
J
3
2J Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Protocol for treatment
Arm-I COP without maintenance
Vincristine
2 750 mgm
2 14 mgm
2 100 mgm
Arm-ll COP with IFN maintenance
as Arm-I regimen)
maintenance IInterferon alfa-2A Mu
Arm-ill I-COP with IFN maintenance
Vincristine
Prednisolone
j ITnterferrn a1fa-2A
2 750 mgm
2 14 mgm
2 100 mgm
6Mu
maintenance maintenance as Arm-II regimen
B) Intermediate grade (lG)
and Hlgb grade (HG)
NHL
Arm-I CHOP-I
Adriamycin mgm
2 Vincristine 14 mgm
2 Prednisolone 60 mgm
alfa-2B Mu
Maintenance alfa-2B Mu
2
middot 4
Arm-n CHOP with COP maintenance
2 Cyclophosphamide 50 mgm
2 50 mgm
2 Vincristine 14 mgm
2
Maintenance Cyclophosphamide
2 Vincristine 14 mghn
2
mgm
60 mgm
Arm-ill CHOP without maintenance
Induction regimen as Arm-IT
C) Other types of NHL Cyclophosphamide
2 Vincristine 14 mgm
2 60 mgm
2 mgm
D) Failure Progrion Relapse or Stable disease
Option 1 ENAP regimen
2 100 mgm
2 10 mgm
2 I~rtnltn arabinoside 100 mgm
2 Prednisolone 100 mghn
Option 2 MINE regimen -----------------~~--------------------~ Mesna mg
2 133 mgm
2 8 mgm
2 Etoposide mgm
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
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21200 3pound1 1 V
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2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
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600 j2n IV ~s~ ey l~
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cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
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trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
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PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
3
2J Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Protocol for treatment
Arm-I COP without maintenance
Vincristine
2 750 mgm
2 14 mgm
2 100 mgm
Arm-ll COP with IFN maintenance
as Arm-I regimen)
maintenance IInterferon alfa-2A Mu
Arm-ill I-COP with IFN maintenance
Vincristine
Prednisolone
j ITnterferrn a1fa-2A
2 750 mgm
2 14 mgm
2 100 mgm
6Mu
maintenance maintenance as Arm-II regimen
B) Intermediate grade (lG)
and Hlgb grade (HG)
NHL
Arm-I CHOP-I
Adriamycin mgm
2 Vincristine 14 mgm
2 Prednisolone 60 mgm
alfa-2B Mu
Maintenance alfa-2B Mu
2
middot 4
Arm-n CHOP with COP maintenance
2 Cyclophosphamide 50 mgm
2 50 mgm
2 Vincristine 14 mgm
2
Maintenance Cyclophosphamide
2 Vincristine 14 mghn
2
mgm
60 mgm
Arm-ill CHOP without maintenance
Induction regimen as Arm-IT
C) Other types of NHL Cyclophosphamide
2 Vincristine 14 mgm
2 60 mgm
2 mgm
D) Failure Progrion Relapse or Stable disease
Option 1 ENAP regimen
2 100 mgm
2 10 mgm
2 I~rtnltn arabinoside 100 mgm
2 Prednisolone 100 mghn
Option 2 MINE regimen -----------------~~--------------------~ Mesna mg
2 133 mgm
2 8 mgm
2 Etoposide mgm
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
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J
~ ~ ~
j gt~
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J6Yi- _
____ _ _ __ _ _c- _ t--~
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
middot 4
Arm-n CHOP with COP maintenance
2 Cyclophosphamide 50 mgm
2 50 mgm
2 Vincristine 14 mgm
2
Maintenance Cyclophosphamide
2 Vincristine 14 mghn
2
mgm
60 mgm
Arm-ill CHOP without maintenance
Induction regimen as Arm-IT
C) Other types of NHL Cyclophosphamide
2 Vincristine 14 mgm
2 60 mgm
2 mgm
D) Failure Progrion Relapse or Stable disease
Option 1 ENAP regimen
2 100 mgm
2 10 mgm
2 I~rtnltn arabinoside 100 mgm
2 Prednisolone 100 mghn
Option 2 MINE regimen -----------------~~--------------------~ Mesna mg
2 133 mgm
2 8 mgm
2 Etoposide mgm
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
c-a Ch - 16( t1 fl v)u -ri ~ N ~ ~ cp )~gt1 L ~r M J ~ f ~ ~lLgt1
~ lmiddot5L1 bull
) l ) C
bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull~middot~bullbullbull ~ bullbullI~~~~~~0~J~bullbullbullbullbullmiddotbullbullmiddotbullbullmiddotbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull ~(Jt~
u u ~ uuu uu
Llt+-~
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
6
Option 3 CMPP regimen
2 650 mgm
50mg
2 Procarbazine 100 mgm
Prednisolone 100 mg
22 Hodgkin bull disease (HD)
A) Previously untreated case
2C-MOPP regimen 750 mgrn
2 Vincristine 14 mgm
2 100 mgm
2 mgm
B) Failure Progression of disease table disease or Relapse
2ABV regirntn 50 mgm
2Vinblastine mgm
2 10 mgm
6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
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tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
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Start 7-21 after last dose of IfTX 1 T
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METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
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6
MYELOPROLIFERATIVE DISEASES
31 Chronic myelogenous leukemia (CML) chronic pbase
2-12 mgday PO
32 Ioterferon protocol in CML chronic ph
Phase I IHYdroxyurea mgkgday PO
Phase II Patients will be randomized into 2 groups
Arm-I 5 MuAlfa-2B
9 If WEC gt 15 x 10 fL add hydroxyurea
2 Mfll1fl1Ut)1JM 3-6 L~VJ L~1J Ara-C 20 mgJl day
Arm-2 Ioterferon alfa-2B 5 Mu
2 Ara-C 20 mgm
33 CML blastic ph
Option 1 Palliative chemotherapy
2 1C1ltolane arabinoside 20 mgm
Option 2 To assess the efficacy of combination of low dose cytosine
arabinoside and IFN in treatment of CML patients with blastic crisis
Ioterferon alfa-2B 5 Mu
2 20 mglmAra-C
804 Other myeloproliferative diseases -----------------------------------------4
mgday PO
Option 2
Phase I
Option I
Interferon alfa-2B
Phase 2 IMamtain with interfon alfa-2B
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
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c
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- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
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trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
7
4 MULTIPLE MYEWMA (MM)
41 Previously untreated cases
A) Conventional therapy
bull
Melphalan
Prednisolone
B) Interferon protocol for MM
Maintenance regimens
Arm-I
Arm-n
Arm-ill
Melphalan
Prednisolone
Interferon alfa-2B
Interferon alfa-2B
Interferon alfa-2B
Dexamethasone
mgday
mgday
2 mgm
42 Failure Progressing Relapsing or Stable disease
Option 1
Option 2
IR~peat cycle every 6 weeks
O4mg
2 9 mgm
40 mgday
6 mgm2
60 mgday
Interferon alfa-2B 3 Mu SC thrice a week
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
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J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
c-a Ch - 16( t1 fl v)u -ri ~ N ~ ~ cp )~gt1 L ~r M J ~ f ~ ~lLgt1
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) l ) C
bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull~middot~bullbullbull ~ bullbullI~~~~~~0~J~bullbullbullbullbullmiddotbullbullmiddotbullbullmiddotbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull ~(Jt~
u u ~ uuu uu
Llt+-~
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
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PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
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I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
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VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
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AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
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600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
8
PROTOCOL FOR MANAGEMENT OF LUNG CANCER
(llfll11i~~IIIlUflnlOlnhtl~I~ h~Y1D1U1aIHD1Umlllri 7111 2587)
A1
A2
A8
81
32
A4 (Etoposide orally)
B1
B2
bull
CispJatin
Etoposide
Carboplatin
Etoposide
IfosfarrUde + Al or A2
2 25 mgm
2 100 mgm
2 25 mgm
2 100 mgm
2 2 gm
Ifosfamide + Cisplatin + Etoposide
Ifosfamide + Carboplatin + Etoposide
VP - 16 50 mg
2 Mitomycin 8 mgm
2 VinblllBtine 45 mgm
2 CispJatin 100 mgm
2 Mitomycin 8 mgrn
2 Vinblastine 45 mgm
Carboplatin (~1IlflIJ HtJ1flfl~llJ ll~))
bull lmiJf)~iiW1n severe neutropenia TYlDlrm Neupogen (G-CSF) 1llJiiU chemotherapy YJnflr~
~
)
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J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
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bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
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c-a Ch - 16( t1 fl v)u -ri ~ N ~ ~ cp )~gt1 L ~r M J ~ f ~ ~lLgt1
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bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull~middot~bullbullbull ~ bullbullI~~~~~~0~J~bullbullbullbullbullmiddotbullbullmiddotbullbullmiddotbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull ~(Jt~
u u ~ uuu uu
Llt+-~
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
~
)
~~l bull ~ bull
J
~ ~ ~
j gt~
-- --=-_ r~Cl-
J6Yi- _
____ _ _ __ _ _c- _ t--~
bull
1lt11
bullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull _ bullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbull bull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbull bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbullbullbullbullbullbull bull bullbullbullbull bullbullbull _ bullbullbullbullbull _ _ bullbullbullbullbullbull 1
J ( ~ ~ -- -I SL lt ~ ---
middotmiddotmiddotmiddotmiddotmiddot middotmiddotmiddotmiddotmiddot middotmiddot middotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddotmiddot~middotmiddotmiddotmiddotmiddot1middot~middotmiddotmiddot~-~middot~I~~~~~~~~~~~ f ~~~ ~~ ~~~~~~~~~~0middot1middot n - tJ I f II r) -
YlSluc CD lut 11gt1---- fY 1~ f - V d c t - l) 5J G) 1 cent f ~
c-a Ch - 16( t1 fl v)u -ri ~ N ~ ~ cp )~gt1 L ~r M J ~ f ~ ~lLgt1
~ lmiddot5L1 bull
) l ) C
bullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull bullbullbull~middot~bullbullbull ~ bullbullI~~~~~~0~J~bullbullbullbullbullmiddotbullbullmiddotbullbullmiddotbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbullbull ~(Jt~
u u ~ uuu uu
Llt+-~
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
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Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
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1lt11
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CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
CANCER PROTOCOL bullDIVISION OF HEMATOLOGY
DEPERTMENT OF INTERNAL MEDICINE
FACULTY OF MEDICINE PRINCE OF SONGKLA UNIVERSITY
1 ACUTE LEUKEMIA
11 Acute non-lymphoblastic leukemia (ANLL) shyA) Previously untreated case
El iglbil ity criteria
~ Adult patient 15 to 60 years old Morphologic proof of ANLL FAB types MI through M7
~ I as determined by morphologyI
No previous treatment with
- ECOG performance status of
- Adequate hepatic and renal - No evidence of Infections
Protocol for treatment Induct ion
and cytochemistry
chemotherapy or radiation
0 I 2 and 3
function
Cytosine arabinoside 100 mgm 2 cont Inuous IV infusion day s 1-7
Adrlamycln 45 mg m2 IV days 1- 3
Repeat cycle middotevery 4 weeks
Criteria for evaluation
Complete remission (CR)
Normal physical status - normal spleen I iver and lymph
node
Normal peripheral blood - Hb ) II gm dL Neutrophils) 15 x 109L
Platelet count) 100 x 109L
MI marrow status - lt 5 blast
) 15 erythroid elements ) 25 normal granulocyte precursors in
a nonhypocellular marrow
Failure complete remission cannot be achieved within
Induct ion courses
~
2
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Postremission therapy
Postremis s ion chemotherapy began 4 weeks after CR It consists of consolidation and maintenance therapy
Consolidation therapy
Cytosine arabinoside 100 mgm 2 continuous IV infusion
days 1-5
Adriamycin 60 mgm 2 I V day s 1
Maintenance therapy
Maintenance chemotharapy began 4 weeks after consoli shydation therapy They will be randomized into 2 regimens to
assess their efficacy in term of survival and disease-free
duration
Regimen A
The intensification therapy with the same regimen as consolidation therapy should be given every 6 months
Regimen B
Cytosine arabinoside 20 mgm 2 SC day s 1-7
6-Thiogaunine 40 mgm2 PO days 1-
Repeat every 4 weeks
Maintenance therapy will be continued for at least years or until relapse occurs
Bone marrow aspiration to detect relapse should be
performed routinely every 3 months for the first 2 years of
follow up period
Drug Toxicity Grading according to WHO criteria
C~iteria for relapse ~
- Appearance of circulating leukemic cells or
- gt 5 blasts in the bone marrow
B) Elder Iy case
S tudy ob~ec t ive To evluate the efficacy of low dose cytosine arabinoshy
side in treatment of a~ute non-lymphoblastIc leukemia in elderly
patients in term of response rate and survival
EligibilIty criteria
Adult patientgt 60 years old
Morphologic proof of ANLL PAB -types Ml through M7
2
2
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
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Deep X--~y ~ lr~e )
c
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VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
as determined by morphology and cytochemistry
- No previous treatment with chemotherapy or radiation
ECOG performance status of 0 I 2 and 3
- Adequate hepatic and renal function
- No evidence of Infections
Protocol for treatment
cytosine arabinoside 20 mg m2 SC days 1-7
Repeat every 4 weeks
C) Relapse or Refractory cas~s
Option 1 Relapse occurs after 6 months from CR
Cytosine arabinoside 100 mg m2 continuous IV infus ion
Ad r iamyc in 45 mgm 2
days 1-7
IV days 1-3
Repeat cycle every 4 weeks
Option 2 Refractory case or Relapse within 6 months from CR
Etoposide 100 mg m 2 IV infusion in I hr days 1-5
Mitoxantrone 10 mgm2 IV day 1-3
Drug Toxicity Grading according to WHO criteria
12 Acute lymphoblastic leukemia (ALL)
Open prospecti ve multicenter study
Songklanagarind hospital
Chulaiongkorn hospital
Maharaj Nakorn-Chiangmai hospital
Pramongkutkloa ho spi tal
Rajavithi hospital
Ramathibodi hospital
Study obJectives
I To determine the complete remission rate survival and disease-free su rvival of adult ALL treated with modified
Hoelzers chemotherapy regimen
2 To determine the factors that are progn os tic for the
achievement of complete remission and disease-free duration
Eligibility criteria ~
- AduLt patient age ~ 15 and ~ 65 years old I
3
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
- Morphologic proof of ALL FAB types Ll L2 L3 as determined by morphology and cytochemistry
- No previou s treatment with chemotherapy or radiation
- ECOC performance sta tus of 0 1 2 and 3
- Adequate hepatic and renal function
- Free of infections
Protocol for treatment
Induction
Phase I
Vincristine 14 middotmgm 2 [V day 181522
(maximal single dose(2- mg)J
Adriamycinmiddot 15 m~[v day 1815 2 2
Prednisolone 60 mg m2 PO day 1-28
plusmn L-asparaginase 5000 Um 2 IV day 1-14
Phase 2
Cyclophosphamide 650 mgm 2 IV day 294357
(maximal single dose 1000 mg)
Ara-C 75 nignG _ [-V day 31-3438-4145-48
52- 55
6-Mercaptopurine 60 mg m2 PO day 29-57
Methotrexate 10 mgm 2 IT day 31384552
(maximum 15 mg)
CNS irradiation 24 Cy day 29-57
Criteria Cor evaluation r
Complete remission (CR)
Normal physical status - normal spleen liver and lymph
node
Normal peripheral blood - Hb ) 11 gmdL
Neutrophils ) 15 x 10L
Platelet count) 100 x 10L
Ml marrow status - lt 5 blast ) 15 erythroid elements ) 25
- normal granulocyte precursors in
a nonhypocellular marrow
Fa i lure complete remission cannot be achieved within
induction cOUrses
I 4
2
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Consolidation
Phase Vincristine I 4 mg m2 IV day 181522
(maximal single dose 2 mg) Adriamycin 25 mg m2 IV day 18 1522
Dexamethasone 10 mg m2 PO day 1- 28
Phase 2
Cyclophosphamide 650 mgm 2 IV day 29 Ara-C 75 mgm2 I V day 31-3438- 41
6-Thloguanlne 60 mgm2 PO day 29-42
Maintenance
6-Mercaptopurine 60 mgm 2 PO daily week 10-18
Methotrexate 20 mg m2 PO weekly and 29-130
The patient will be followed every months after completing
chemotherapy Bone marrow aspiration should be performed every 3
months
Drug Toxicity Grading according to WHO criteria
2 MALIGNANT LYMPflOMA 21 Non-Hodgkin Lymphoma (NHL)
A) Low grade NHL
Open randomized prospective multicenter study
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chaingmal
Pramongkutkloa hospi tal Bangkok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives
To evaluate the addition for combination alfa Intershyferon (IFN) to a three-drug chemotherapy regimen (COP) for low-
grade NHL with respect to objective response rate toxicity
duration of response and survival
EIlglbillry criteria - Biopsy proven diagnosl$ of malignant lymphoma of one
of the following histologic subtypes as per the
International Working Formulation
Diffuse lymphoma small lymphocytic
Diffuse lymphoma plasmacytoid lymphocytic
~-
5
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
x
Follicular predominantly small-cleaved
Follicular mixed small c leaved and large-cell
Mantle zone lymphoma Monocytoid B-cell lymphoma
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter - WBC count) 40 x 10 f L and platelet count) 100
10- f L except for marrow invasion
- No previous treatment with chemotherapy or radiation
- ECOG performance i tatus of 0 I 2 and 3
- Adequate hepatic and renal function
- No ev idence of infec t ions
( J I
PraLocol f~gtr treatment fArm-I COP wlthout maintenance Irrdh c t ion
Cyclophosphamide 750 mgm 2 IV day I
Vincristine I 4 mgm 2 IV day I
Prednis o lone 100 mg PO day 1- 5 Repeat cycle every 28 days x 8 courses
A rm- I I COP with rir~ maintenance shy
I
-1- COP as Arm-I regime~) Maintenance ( Interferon aIfa-2A 3 Mu SC thrice weekly for 12 months $ tar t ed from achievement of CR PR or SD to disease
progression re lapse or patient off s tudy therapy
Arm-I I I I-COP with IFN maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Vincristine I 4 mgm 2 IV day 1
Prednisolone 100 mg PO day 1-5
~ Interferon aIfa-2A 6 Mu SC day 22-26
Repeat cyc I e every 28 days x 8 courses
lIa In tenance v IFN main tenance as Arm~1 I reg 1m en
(
f- c I
6
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Criteria for evaluation
Complete response (CR) - Disappearance of all measurable
or evaluable disease symptoms signs and
biochemical change related tumor
Partial response (PR) ~ A reduction gt 50 in the sum of
products of two perpendicular diameters of all
measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 increase
in the sum of products of two perpendicular
diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase in the products of two perpendicular diameters of a
measured lesion by ) 25 over the size present at
entry of study and or the appearance of new areas
of disease
Drug Toxicity Grading according to WHO criteria
B) Intermediate grade (IG) and High grade (HG) NHL
Open randomized prospective multicenter study
(Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla
Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Prarnongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study objectives I To compare and contrast the duration of survival of
pat ients with IG HG NHL treated with the study CHOP-I CHOP with
COP maintenance or CHOP regimens
2 To compare and contrast the rates and duration of
objective response or stabie disease in patients with IGHG NHL
treated with thestudy CHOP-I CHOP with COP maintenance or CHOP
regimens
Eliglbiiity criteria - Biopsy proven diagnosis of malignant iymphoma of one
of the foilowing histoioglc subtypes as per the
International Working Formuiation (IWF)
7
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Intermediate grade
Follicular predominantly large cell (IWF-D)
Diffuse small cleaved cell (IWF-E)
Diffuse mixed (IWF-F) Diffuse large cell (lIiF-G)
High grade
Diffuse immunoblastic (IWF-H)
- At least stage II (Ann Arbors) diseases
- At least one objective measurable diseases parameter
- WBC count) 40 x 109 L and platelet count) 100
109L except for marrow invas ion
- No previous treatment with chemotherapy or radiation
- ECOC performance s tatus of O I 2 and 3 - Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Arm- I CHOP- I
Induction
( Cyclophosphamide 750 mg m2 IV day I
Ad r i amy c in 50 mg m2 IV day I
Vincristine I 4 mg m2 IV day I
Predni so lone 60 mgm 2 PO d3y 1- 5
Interferon alfa-2B 5 Mu SC day 22-26
Repeat cy c I e eve ry 28 days x 8 courses
Maintenance __ -- -----~ ~terfer~n alfa-B 3 Mu ) three times a week for 52 weeks
from achievement of CR PR or SD or patient off study
therapy
Arm- I I CHOP wit h COP maintenance
Induction
Cyclophosphamide 750 mg m2 IV day
Adr larn~c In 50 mg m2 IV day
Vincristine I 4 mgm2 IV day I
Predn I so lone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 8 courses
Maintenance1 CyclophosphamIde 750 mg m2 IV day
Vlncrlstln~ 1 4 mg rc 2 IV day I I
8
x
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Prednisolone 60 mgm 2 PO day 1-5
Repeat cycle every 28 days x 12 cOUrses
A rm- I I I CHOP without maintenance
Induction CHOP regimen as Arm-II
Criteria for evaluation Complete response (CR) - Disappearance of a 11 measurable
or evaluable disease symptoms signs and biochemical change related tumor
Partial response (PR) - A reduction gt 50 in the sum of products of two perpendicular diameters of all measurable lesions
Stable disease (SO) - A lt 50 reduction and lt 25 Increase In the sum of products of two perpendicular diameters of all measurable lesions
Progression of disease of Relapse (PO) - An increase In the prodUcts of two perpendicular diameters of a measured lesion by ) 25 over the size present at
entry of study andlor the appearance of new areas of disease
Drug Toxicity Grading according to WHO criteria
C) Other types of NUL
Cyclophosphamide 750 mgm 2 IV day Adr iamyc in 50 mgm2 IV day
Vincristine I 4 mgm 2 IV day
Prednisolone 60 mgm 2 PO days 1 5 Repea t cycle every 23 day s x 8 courses
DJ fai1uf bull Progression Relapse or Stable disease
Opt ion 1 ENAP reg fmen -~ EtopOSide 100 mgm 2 IV infus ion days 1- 3
Mitoxantrone 10 ill g 1m2 IV infusion days 1-2
Cytosine arabinoside 100 rog IV infus ion days 1-2
Prednisolone 100 mg PO days 1-3
Repeat cycle every 28 days
I 9
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Op t ion 2 MINE regimen ltj
Me sna 400 mg IV every 4 hr day s 1-3 Ifosfamide 1 033 gm 2 IV days 1- 3
Mi toxan trone 8 mgm 2 IV day I
Etoposide 65 mgm 2 IV day s 1-3
Repeat cycle every 28 days
Option 3 CMPP regimen
Cyclophosphamide 650 mgm 2 IV day I 0
Methotrexate 50 mg IV day 1 Procarbazine 100 mg m2 PO day s 1-7
Prednisolone 100 mg PO da y s 1-7
Repeat cycle every 28 days
22 Hodgkins disease A) Previously untreated case
C-MOPP regimen
Cyclophosphamide 750 mgm 2 IV day I 8
Vincristine I 4 mgm 2 IV day I 8
Procabazine 100 mg m2 PO day 1- 14
Predn iso lone 40 mg m2 PO day 1-14
Repeat cycle every 28 days x 8 courses
Criteria of evalution as NHL
B) Failure Progression of disease Stable disease or Relapse
ABV regimen
Adriamycin 50 mgm 2 IV day
Vinblastine 6 mg m2 IV day
Bleomycin 10 mg m2 IV day
Repeat cycle every 28 days X 8 courses
3 MYELOPROLIFERATIVE DISEASES 31 Chronic myeltlgenous leukemia (CML) chronic ophase
~usulfan 2-12 rogday degPQ---3-lti2usted to WEC count
32 Interteron protocol In CML chronic phase
Open randomized prospective multicenter study~O o
Songklanagarlnd hospital Songkhla
Chulalongkorn h~spital Bangkok
010
j
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
-- -
)
Pramongkutkloa hospl tal Banglok Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok Srinagarind hospital Khon Kaen
Study objectives
1 To compare and contrast the hematologic cytogenetic
responses and survival in CML patients treated with interferon alfa-2B or IFN with low dose cytosine arabinoside
2 To assess the efficacy of combinationmiddot of low dose cytosine arabinoside and IFN in those patients not achieving complete hematologic response (CHR) or cytogenetic response (CCR) by IFN treatment alone
3 To study the side effect profiles of interferon alfa-2B in these study populations
Eligibility criteria - All patients age lt 65 years with chronic phase of Ph 1 shy
positive CML Previously untreated with cytotoxic drug (except In the
case of busuifan If iess than 7 days duration or hydroxyurea for less than 12 months)
- ECOG performance status 0-1 - Adequate hepatic and renal function
- No evidence of infections r
_ I I r Protocol for treatment
i IPhase Hydroxyurea 50 mgkgday PO
The dose should be adjusmiddotted unt i I the WBC Is lt 15 X 109
per litre
Phase II Patients wIll be randomized into 2 groups
Arm-I
Interferon alfa-2B 5 Mu SC thrice a week or that dose
which will maintain the WSC around -I x 10L until CCR I s produced and maintained for the duration of a minimum of 12
months
AI If WSC gt IS x 10L add hY9Joxxurea Patients not achieving a CHR within 3 months or CCR at
6 months will be considered for the addition of Aia-C 20
gt I I
bull f bull bull bullbull
- shy~
~~ itmiddot gt
-
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
mgm 2 day SC for 12 days each mon th un til a CCR is obta ined ~0
and then maintain for 12 months
Arm-2 Interferon alfa-2B 5 Mu SC thric e a week
Ara-C 20 mgm 2 SC for 12 days each month Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Criteria for response
Hematological response Complete hematologic remission (CHR)
Normalization of peripheral WBC counts to levels lt 10 x 10
per litre with normal differential counts normal platelet
counts and disappearance of all clinical symptoms and signs
of disease including splenomegaly Partial hematologic remission (PHR)
Decrease in WBC to at least lt 20 x 10L ( ) 50 from preshy
tre~tment) and of platelet counts and reduction by more than 50 of splenomegaly
Cytogenetic response
Complete cytogenetic response (CR)
Hematologic and clinic~l remission with Ph chromosome in
marrow metaphase lt 1
Partial cytogenetic response (PR)
Ph chromosome suppression was to levels of 1-34
Minimal cytogenetic response (MR)
Suppression was to le ve ls o f 35 to 95 of metaphases
No cytogenetic respons e (NR)
Ph chromosome per s isted in ) 95 of analyzable metaphase s
Drug Toxicity Grading ac cor ding to WHO criterIa
33 CML blasti~ phase Optio 1 paillatl v-=--chemotherapy
j cytoslne arabnoside 20 mg m2 SC days 1-10
Repeat every 4 weeks
Option 2 Tqass sect~ the efficacy of comblnat ion of low dose
cytosine arabinoside and IFN In treatment of CML patients with 1
12
(J1(
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
blastic crisis Interferon alfa-2B 5 Mu SC thrice a week
Ara-C 20 mampm 2 SC for 10 days each month
Hematologic response should be evaluated at the end of
3 months and cytogenetic response at the end of 6 months
Cr iter ia for response Complete remission
Normal physical status Normal peripheral blood (Hb ) 11 gdL neutrophils ) 15
-
x 109 L platelet count) 100 x 109 L)
MI marrow status lt 5 blast ) 15 erythroid elements ) 25
normal granulocytic precursors In a nonhypocellular marrow
Failure complete remission cannot be obtained within 3
inducti on courses
Drug Toxicity Grading according to WHO criteria
34 Other myeloproliferative diseases (Polycythemia vera
Essential thrombocythemia) OptIon 1
Busulfan 2-12 mgday PO adjusted to WBC count
Opt ion 2 -
Phase I - Interferon alfa-2B 3 Mu SC thrice a week
Criteria for response Polycythemia v era
Complete response - A normalization of the hematocrit level laquo 48) in the absence of further phlboshy
tomy WBC count platelet count within 16
weeks of treatment and maintained for at least 2 months without clinical symptoms
or palpable spleen ~
Partial response - Persistence 6f any the following Hct ) 48 or Hb gt 16 gdL WBC ) 10 x 109L
platelet ) 400 x 109 L spleen 1-5 cm
below left costa l margin
I 13
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
No response - no change or disease progression
Essential thrombocythemia Complete response - A reduction of platelet count to lt 450 x
10middotL within 16 week of treatment and
maintained for at least 2 months without clinical symptoms or palpable spleen
Part ial response - A greater than 50 reduction in spleen and decrease in platelet count less than
the levels for CR No response - no change
Phase 2 - Maintain with interfon alfa-2B 5 Mu twice a week
after CR till 12 months
I 4 MULTIPLE MYELOMA (MM)
41 Previously untreate cases
A) Conventional therapy Melphalan 6 mgm 2 PO days 1-4 Prednisolone 60 mgday PO days 1- -I
Repeat cycle every 6 weeks
B) Interferon protocol for MM
Open randomized prospective multicenter study (Asian Investigators Multi-center Studies AIMS-Thailand)
Songklanagarind hospital Songkhla Chulalongkorn hospital Bangkok
Maharaj Nakorn-Chiangmai hospital Chiangmai
Pramongkutkloa hospital Bangkok
Rajavithi hospital Bangkok
Ramathibodi hospital Bangkok
Study obJectives
I To compare a~d contrast the durations of objective
responses of patients with MM recieving the protocol maintenance
regimens 2 TO-compare and contrast the durations of survival of
patients with MM recleving the protocol maintenance regimens
Eligibility criteria
- Durie-Salmon stage II or III M~I
- ECOG performance status 0 I 2 and 3
- Patients may not have recleved any prior system Ie
14
middot r
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
middot
anti-MM therapy
- Adequate hepatic and renal function
- No evidence of infections
Protocol for treatment
Induction regimens
Melphalan 6 mgm 2 PO days 1-7
Prednisolone 60 mg m2 PO days 1-7
Repeat cyc le every 28 days for 6 cyc les
Criteria for resp ons e
Complete response - all of the following Disappearance
of serum andor urine M pr ote in on two
determinations at least 4 weeks apa r t Normal marrow with lt 5 plasma cells
normal peripheral blood and no sign s
or symptoms normal calcium and resolution of all soft tissue plasmacytoma
Objective response - all of the following Redu c tion of
serum M protein iovels to ~ 50 of baseline leve s on two determintions
at least 4 weeks apart decreased plasmacytoma by ~ 50 the sum of the
produ c ts of two perpendicular
diameters de c rease in bone pain
Stable disease - Failure to meet respon se c riteria of
complete remi ss ion objective response
and disease progression
Relapse or Progress ion - any of the following
- Inc rease In serum M prate In leve I to ) 50 abo ve
lowe s t remission level
Increase in urinary M protein level to) 50 abo v e
lowe~t remi ss ion level - Appearance of new ___ plasmacytomas or increase in
pla smacyto mas by 50
- Appearance of new lytic bone lesio ns or a ) 50
increase In the s ize of any existing lesion
Failur e or Resistance When compared with basel ine va lues
a ) 50 In th~ serum or urinar y M-pr o tein 1evels
15
7
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
measured on two determinations 2 weeks apart having
recieved 3 cycles of therapy
Maintenance regimens Patient rand omization into 3 groups
Arm-j
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Arm-II Interferon alfa-2B 3 Mu SC thrice a week for year
from objective response
Arm-Ill
Interferon alfa-2B 3 Mu SC thrice a week from objective
response to disease relapse
Dexamethasone 25 mg m2 PO for 4 days every 28 days
from objective response to
disease relapse
Drug Toxi city Grading according to WHO criteria
42 Failure Progressing Relapsin g or Stable disease
Option 1 Pamiddottjents recieving either from 41 A) or 41 B)
Vincrist ine 04 mg IV continuous infu sion days 1- -l
Ad r I amyc in 9 mg m2 IV continuous infusion days
1-4
Dexamathasone 40 mg d PO days 1-4 9- I 2 17-2 0
Repeat cycle every 4 weeks x 6 courses
Option 2 p~r-ents~cieving regimen 41 A)
Melphalan 6 mg m 2 PO days 1-4
Prednisolone 60 mg day PO days 1-4
Repeat cycle every 6 weeks
plus Interferon alfa-2B 3 Mu SC thrice a week
16
( shy
ifiit g J ~ IiW bull I ~
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
-shy0J
PROTOCOL FORmiddot WI IS TUMOR
st I FAVORABLE AND UNFDVCRAB HiSlDLOGY
5d A~d A~ d 5d
ACTINOMYCIN ~ v v
ISTINE vvvvvvvvvv V V
I ) 1 I I I J I NO FUR1HER Rr WEEKS 0 2 4 6 6 10 13 26
AMD + VCR 6 Mv
ACTINOMYCIN = 15 mltgIgd( 1 v ) c ) I
VINCRISTINE 1S mgtr-waek (Lv)
shy
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
PROTOCOL FOR I S TUMOR------------------ltltlt --lt-shy
st II FAVORABLE HISTOlOGY
~d gt ~d ~d ~d ~d ~d ~d ~ n n n
i u U U U ~ U U U
R1SiNt fVyvvvvvvv YVVVYV vvvvyenv yenltvvvv V VVVy v vvvvvv vvv VYV
WEEK 0 2 bull 6 6 12 22 )1 40 49 ~8 6~ ~ 7 9 I ~
AID VCR 15 Mo bull
bull ACTINOMYCIN 15 mcgkgd (1 v ) 2
bull VINCRISTINE = 15 mgM Week (iv)
~
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
bull ~ItI~~ -
bull f bull It
~~~~~~~ ~ i ltI
~ ~tI~ ~
PROTOCOL FOR WILMS TUMOR
s1 ill FAVORABLE HISTOLOGY
d d do ~ d ~d amplORIAMYCIN ~ ~~ ~ ~d bull ~ 0 ~
~d ~
ACTINOMYCIN ~ ~ W ~ ~ bull
VINCR ISTINE VV VVVV v vvy V I V V V V V Y V V V
bull I ( I 1 I I J I I bull I 1 f
WEE KS o 2 bull 0 B 10 12 19 26 ~ ~9 4~ ~2 ~e 6~
) ~ 7 9 II I ~
I
I i
lIMO + vcr + ADR 1 5 ~Io + RT 1000 cGy
ICTINO~YCIN = 15 mcgkgd ( iv )
I 2VINCRl iT INE = 1 5 mg M week (iv)
2ADRIAMYCIN 20 mg M d (i v l
shy
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
~1 I
l i
Y _ 1~
-= ~ ~ ~
I
PROTOCOL FOf~ WILM I S TUMOR
----------- - -
st TIl FAVORABLE HISTOLOGY
~
dO do dO dO dO
AORAMYCIN
u U U ~ ~ I ~O ~o bull ~ 0 ~ 0 ~ 0 ~O
AC1NOMYCIN ~ U U U ~ ~
VVVVVVVVVV V V I V VVINCRITINE V V V V
I I I I I I
WEEKS C 2 6 a 10 12 19 26 ~2 ~9 ~ ~2 ~B 6~
AMD + VCR + ADR 15 Mo + RT 000 cGy TU
+ DISTANT METASTASIS (PULMO~Al1Y) RT 1200 cGy
I lCTINOMYCIN 15 mcgkgd (iv)
I 2VINCRISTINE 15 mgM wcek (iv)
2ADRIAMYCIN 20 mgM d (iv)
I
cOshy
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
----- -
I
PROTOCOL FOR WILM S TUMOR
UNFAVORABLE HISTOLOGY st II-TIl
3 ~d 30 bull 3d
ADRIAMYCIN ~ ~ Q ~ 3~~d Ji)d J ~d 1)d )~d J~d J3d
CYCLOPHQSPHAMIO( ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ 1 ~ 3d
ACTINOMYCIN ~ ~ ~ ~ ~ VvVVvvyvVV V vv V VV v w v
VINCRISTINE V V y V
If I 1 [ I J I I I [ I [ I J l
WEE KS deg 2 4 6 6 10 12 19 26 32 39 ~ 32 ~5191~
c
RTMD + VCR + ADR + CPM 15 10_ age
Pqe (M o ) TOTAL TUMOR DOSE
2 PCTINOMYCIN 15 mcg k~d ( iv)
BIRTH - Ii 1 26 0 - 1800
ADRIMYC IN ~ 20 mgM2~d (iv)
VINCRISTINE I 5 mgM i week (i v )
13 - 1middot~ 2160
CYCLOPHOSPHMIDE 10 mg kg d ( iv ) 19 30 2700
31 - 40 314 0
4 1 t 3780
11
) ~d
~ 3
~ ~
~
~
Vy V Y
I I I
36 63
(cGy)
q
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
Staeinz of NHL
Stage xtcni f tumor
A siqgle ltIor (c~~ronoCal) or sinlc ltlni1torlic
~re) (nod)l) ~ith the cycl u sion of oledistinw
1 A single turor (etranodal) lith reeional Lll
involvei~nt
Tvo sinele (extranodal) tu~ors ~ith or without
~e~ionQl LN involvewen on the same side of the
A resecta~le prinary Cl tract tu~or usua ll y In
the ilpocecil areal lith or ithout involvenent
of the C5s ~iate~ fCscnteri~ nodes oilly
TJo single tUlilors (etranodal) on oiJ~oslte ides
of the diaph=ag3
To or LlOre nodal oreaz above or belo the
diaj)hraga
~ll the pr~zry intrJthoracic tU~IDr
(nedias t ind gt pleur B 1gt thymic)
All extensive prioar~ intro2bdomin~1 ~sease
tll p~r3spin~1 Or e~idura l tumorc rC8~rdless of other tuors it~ (or sites)
IV Any of tle aoove with initial involvement of eNS
o~ bone m~rro~ or bbth
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
conp Protocal
CTX
l
Haincanance
crx
HI
mx
PRW
IITotal
ll shy
21200 3pound1 1 V
~2 1 V ~
2 mgJfl r-
3134 2
rrgJ~i I ~ V
(60l IV push 40 IV drip io
4 hr)
60 mgNJd PO off
Start 7-21 after last dose of IfTX 1 T
1000 rgH2 LV q 28 d
15 L
flgJ~ LV D1 q 28 d
625 2
OBit LT D 29
q 28 d
300 2
mgl LV D15
-q 28 d
60 2 3H d Po x 5 d D29 lt 28 d
duration of theran 13 months fl
Keep Ie l500cumm
I
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
2 HOdeJltin S
- Lfilphotla
l St-ee I - RdiotherlPY cr uep X-roy Ledly
b StltcE Il + III v I v
1 1-~lfJrtm~Jn1pJtmiddot X--y v
fYJ
11_1 ttJ02 S tc2UE
2 v
Cht~cmiddott~euror~rY l ~i1i5-J11)t ~ v
Deep X--~y ~ lr~e )
c
PrEeniscJ(2 2 ccfltJ () r 14 c lo) vL I-t 6---hshy
VCR J
- ( I J
-2 - DiJ-kdIi - o _f e r 14 t
600 j2n IV ~s~ ey l~
15 rbulljimiddotshy I V ush doy 1 W I ~
cu-se l middotLiijll~U li ll~ l(l 2 - 3 ~ bull I Y
8
6
Stieuro TJ l YJJrnu C-f~middot tEr y l J l-~middot~limiddot~J ~ fi0j middotDrP VI poJ
trut_e~t l1-lnhot)i-)JIIFl1 1114 5 U
lt Inri
1 -
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l
o ~tJYi 4 d6maan~lbULJ MODIFIED CCC IU4 UNtiKLA I JltII
PHASE I PHASE II
o 7 14 21 28 r 14middot 21 2e 33 IIDAYSc middotmiddot
8M 8r~ 8M 11IIJIIJliIIjllJj CR i~N1AL RADIATION 1866 cGy
VCR 15 mg rt()t t t t [~ - - -
PRED 40 mgl Iff I dPO I
METHOTREATE reg io mg Age 24-36 Mo T MTX () T f T 12 mg Age gt3 yrs
6 MP 75 mg I ItI dPO
PHASE m o r I
2 I
3 4 5 I 6 1 a 9 I 10 I
II 120I WEEKS
~ ~)~ ~~
t 2 VCR 15 mg I in 8M
T MTX () 8) 10 or 12 mg 2 I
I I PRED 40 mglm I dPO FOR 5 DAYS
M M M M M I M M M M
I M M M
Ar-r o-I-h 0shy
CMTX 20mg 1M lwk PO) I ~
r= r ---shy-- __ _-----shy -shy --shy
I 2 6 MP 75 mgl M IdPO
~~~ ~~ I middot II bullgt~middot ~1~~ f~~~~gt~~~~~~~~middot[ REPEAT CYCLE EVERY d WEEKS FOR 3 YEARS ] i
I l