14/01/15

In The Name Of In The Name Of GodGod

خداوند نام خداوند به نام بهبخشاينده بخشاينده گرگربخشايشبخشايش

Evaluate the combination ofEvaluate the combination of Irinotecan Irinotecan andand Capecitabine Capecitabine in the first line treatment of in the first line treatment of

advanced or metastatic gastric advanced or metastatic gastric cancercancer

Dr.M.DorchinDr.M.DorchinClinical OncologistClinical Oncologist

Dezfol University of Medical SciencesDezfol University of Medical Sciences

BackgroundBackground

Gastric cancerGastric cancer• SecondSecond most common cancer-related death. most common cancer-related death.

• 44thth most common cancer most common cancer• Korea, Japan, China, Taiwan high rates.Korea, Japan, China, Taiwan high rates. with with 875,000875,000 injured annually person in the injured annually person in the

world.world.

Palliative chemotherapy with:Palliative chemotherapy with: Irinotecan and cisplatin.Irinotecan and cisplatin. Folic acid, 5-FU, and irinotecan (Folic acid, 5-FU, and irinotecan (FOLFIRIFOLFIRI).). Leucovorin, 5-FU, and oxaliplatin (Leucovorin, 5-FU, and oxaliplatin (FOLFOXFOLFOX).).

Phase II Phase II studies evaluating studies evaluating irinotecan-basedirinotecan-based or or oxaliplatin-basedoxaliplatin-based regimens demonstrate regimens demonstrate similar responsesimilar response rates rates

Treatment options under clinical evaluation:

Second-Line Therapy in Gastric CancerSecond-Line Therapy in Gastric Cancer

** 20-40% patients receiving 1 20-40% patients receiving 1stst-line -line therapy receive 2therapy receive 2ndnd-line-line

** Taxanes(weekly paclitaxel)and Irinotecan most commonly used 2nd-line therapy…..

Progression Free SurvivalProgression Free Survival

)Months(

Pro

bab

ilit

y )

%(

2 .33.6

108111

6646

1618

98

36

22

wPTXIRI

Number at risk

21

00

00

IRI

wPTX

n

111

108

Median

2.3M

3.6M

P

0.33

HR (95% CI(

1.14( 0.88-1.49)

Log-rank test

FAS

IRI150 mg/m2 d1, 15 q4w

weekly Paclitaxel80 mg/m2 d1, 8, 15 q4w

Irinotecan vs. Best Supportive Care in Second-line Gastric Cancer

Thuss-Patience et al. ASCO 2013

Irinotecan 250 mg/m2Irinotecan 250 mg/m2 q 3weeks

Best Supportive CareBest Supportive Care

MedianMedian SurvivalSurvival

4.1 mo

2.4 mo

P = 0.02P = 0.02HR = 0.48 (95% CI, 0.25-0.92HR = 0.48 (95% CI, 0.25-0.92((

NN21

19

Fig. 2 Overall survival (intention to treat population) Median survival Irinotecan: 4.0 months, BSC: 2.4 months; one sided logrank test: p =

0.012; HR: 0.48 (95% CI: 0.25–0.92).

Peter C. Thuss-Patience , Albrecht Kretzschmar , Dmitry Bichev , Tillman Deist , Axel Hinke , Kirstin Breithaupt ,...European Journal of Cancer, Volume 47, Issue 15, 2011, 2306 - 2314

AIO: Small trial of irinotecan vs BSC

INCREASED EFFICACYINCREASED EFFICACY

Compatible side effects

Different mechanisms of resistance

ACTIVITYACTIVITY SAFETYSAFETY

Aim of combination therapy

Different mechanisms of action

Patients & methodsPatients & methods:: The size of the sample assessed The size of the sample assessed 849849 patients, patients,

and has been started accepting patients in and has been started accepting patients in SyriaSyria (Damascus) in July of (Damascus) in July of 2007, and begin accepting , and begin accepting patients at the Center for patients at the Center for Al-BairouniAl-Bairouni UniversityUniversity HospitalHospital in June of in June of 2009, and , and ended up accepting patients in December of ended up accepting patients in December of 2011, and from scheduled follow-up of patients , and from scheduled follow-up of patients follow-up up to follow-up up to two yearstwo years..

Statistical AnalysesStatistical AnalysesTable 1 shows total new cancer cases referred to the Al-Bairouni Table 1 shows total new cancer cases referred to the Al-Bairouni

hospital from 2007-2009hospital from 2007-2009::

Year New cases

GI cancer patients

Gastric cancer

Percentage

2007 9058 758 218 2.4%

2008 9774 874 289 2.9%

2009 10323 963 342 3.3%

07 - 09 29155 2595 849 2.9%

Al-Bairouni University HospitalAl-Bairouni University Hospital

Method:Method:

Irinotecan 180mg/m2 IV d1 Irinotecan 180mg/m2 IV d1

Capecitabine (Xeloda) 1000 mg/m2Capecitabine (Xeloda) 1000 mg/m2

orally bid d1-14orally bid d1-14

Repeat cycle every 3 weeks for 6 cycles.Repeat cycle every 3 weeks for 6 cycles.

Monitoring follow-upMonitoring follow-up:: Text of the protocol to conduct Text of the protocol to conduct clinical clinical

examinationexamination, and a full assessment, the patient , and a full assessment, the patient responsive to treatment, and responsive to treatment, and every three months after the end of treatment, while the after the end of treatment, while the remaining patients, is up to watch them, and remaining patients, is up to watch them, and assess their condition, when they visit the assess their condition, when they visit the hospital, and in order to hospital, and in order to assessassess the the survival survival CollegeCollege..

Age DistributionAge Distribution

Geographic DistributionGeographic Distributionprovince patient percentage

Damascus 390 41%

Countryside of Damascus

118 13%

Aleppo 115 13%

Homs 87 9%

Dar,a 59 6%

Lattaquieh 58 6%

Hom,a 8 3%

Tartoos 5 3%

Al-Reke 5 3%

Al-Sowida 4 3%

Total 849 100%

Results

390

118115

87

59

58

8%5 5 4

θ Ωϖ ϣ

έϒϳθ Ωϖ ϣ

ΐ ΣϠ

κ ΣϤ

ΎϋέΩ

Δ Ϋϴϗϻ

ΓΎΣϤ

α ρήρϮ

Δήϗϟ

Ϊ δ ϳϮ ϟ

The most patients were from Damascus and Aleppo provinces and seaboard patients were the less.

Family HistoryFamily HistoryFamily History Patient Percentage

F.H positive 51 6%

F.H negative 798 94%

Total 849 100%

Smoking & AlcoholismSmoking & Alcoholism

Smoking Patient Percentage

smoker 688 81%

No smoker

160 19%

Total 849 100%

Alcohol user

Patient Percentage

Alcoholism 101 12%

Non Alcoholism

748 88%

Total 849 100%

Presented by intern 張家維

ConclusionConclusion::

Participation is therapeutic, which combines Participation is therapeutic, which combines both of the following drugs :both of the following drugs :

irinotecanirinotecan, and , and CapecitabineCapecitabine, treatment , treatment plans of the most promising in the treatment of plans of the most promising in the treatment of advanced cancer of the stomach or in transition, advanced cancer of the stomach or in transition, where the response rate was recordedwhere the response rate was recorded

objective response is goodobjective response is good & & acceptable side effects well-toleratedacceptable side effects well-tolerated..

Dr.HossamDr.Hossam(Head of Damascus Cancer Center)(Head of Damascus Cancer Center) Dr.Chams-addinDr.Chams-addin(Head of GI Center)(Head of GI Center) Dr.Majdi-ZinDr.Majdi-Zin(Head of Radiation Oncology Center)(Head of Radiation Oncology Center)

Our Group Our Group Al-BairouniAl-Bairouni cancer center cancer center

Damascus University Damascus University

ReferencesReferences::

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Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of Cullinan SA, Moertel CG, Fleming TR, et al.: A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, advanced pancreatic and gastric carcinoma. Fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA 253 (14): 2061-7, 1985.  [PUBMED Abstract]and mitomycin. JAMA 253 (14): 2061-7, 1985.  [PUBMED Abstract]

Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin Ohtsu A, Shimada Y, Shirao K, et al.: Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003.  [PUBMED Abstract]Oncology Group Study (JCOG9205). J Clin Oncol 21 (1): 54-9, 2003.  [PUBMED Abstract]

Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric Waters JS, Norman A, Cunningham D, et al.: Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.  [PUBMED Abstract]cancer: results of a randomized trial. Br J Cancer 80 (1-2): 269-72, 1999.  [PUBMED Abstract]

Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted Ross P, Nicolson M, Cunningham D, et al.: Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol 20 (8): 1996-2004, 2002.  [PUBMED Abstract]Clin Oncol 20 (8): 1996-2004, 2002.  [PUBMED Abstract]

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