382

101

383

DOSE-INTENSITY ESCALATION STUDY OF THE CDE REQIYEN COMafmD WITH Q-CSP WVlW OR WITHOUT PROPHYLACTIC ClPROfLOXAUN IN (RULL CELL LUNG CANCER (SCLC).

G.LMariani, A.Ardirzonl, C.Pennucci, M.Danova’. ACinquagrana’, G.Cilorgl,~Ventwi~,F.RPo’,R.Rorso.Dept.Med.Oncol.I-isWuto~sz~perla z=ai Cancm and ‘LX@. Pnaumokgy S.Maitim Hos@al , V.b Ben&e110 XV,

Qmoa, iTALY. “Internal M&l Dept. Unh,emlty of Pavia, ITALY cD&nacMlesbndardrs@fmmfofam tree~wnt of sac. ~etm~pecti~ studiaa indkxtq pcasibb wrrelatbn m CM dose-intensity (Di) and cllnlcal Mcoma. WebfiVeprevbuslySha*nth#

prPphyacncumofGMCSFbydal~chemoti!erapyavery 2mwrltsinsteed~every3weeks.(EurJCa~29:887,1993).~presenttrialwas aimed at identifying the max&num tolerated dose-intensity (MTDI )oi an ambuiatory CDE rsdman reDeated at Z-rveek IMervais with G-C-SF 5 t&ko davs Cl 1, thmuohout e phase I doskcab~bn study. At each dose level’; 10% &se In&ease-was for-. E&d&en mvbusiv unbeatad Datbnts with 8CiC. am < 70. PS < 2. LI)=lO pfsandE~wen,~.~~weretreatedatMeiirstdose-~~l(’CllM) &, 050 I&J#. E 330 tr~h2) Mthoul any dose-Mting toxkzlty. At the second dcee-ievai (C 1200 m9Id, A 55 irq/n?, E 120 ms/m2) fabtfla neulmpsnia (FN) was the &se-limit& &dciiy (DLT) in 3 out of 5 pet!ents. wbn ~8s resumed by adding ~xacin 500 mg b.i.d. orally on the same days of G-C8F. With the antibbtk pophyfaxis. the second dom-bvel resuited feasiMs with only 114 patients devbloplng FN. Further doss+scatatbn was not possible even with cipfofioxacln prophVtaxisstnce3/6petienfshthsthlrddos&veidavakqedFN(nMhdccummted otai candldclsis in hvo of them) and 116 davefopat severs Herpes i!oster infection. Severs CIJmIMtive thrcmbocytofm& was aiso observed after the third course of ~raatrnsnt. Othar toxicltim ware ns@#bb. Ail evaiuabis patients responded to the treetnX3ftt (6 CR and 10 RP). In conclusbn: 1) ths MTDI of CDE wr&irwd wtth G-C-SF krC1100mghn2,D50nr((lm2,E330msmi!q14ds~wnespardi~toa66%DI increass ov(Ir Me standard schedule, 2) the MTDI ol CDE mMinsd with G-C8F and ~lnisClXK1~,A56mO’m2,Elpnrghn2ql4dayscorcespondlngto a 81% D.I. Increase. These dose-intenshm ragirnans am fear&is on an outpatient beds and coukl be conQared to the standard schedub to prosfmctiiely msess the imlm.3 ol dose_intensHy in SCLC.

384

A PHASE n STUDY OF CYCLOPHOSPHAMIDE I ADRIAMYCIN I

VINCRISTINE I ETOFOSIDE (CAVE) ALTERNATING WITH CISPLATIN / ETOPOSIDE(FE) IN SMALL CELL LUNG CANCER (SCLC)

N. Hara, Y. Ichinose, M. Kuba, Y lchikawa, K. Ninomiya, K. Shima, H. Yamamoto, M. Ohta, and N. Ogawa. Kyushu Lung Cancer Study Group in Japan

It has been demonstrated that etoposide-based chemotherapy can prolong survival in SCLC In this study, we attempted to determine whether CAVE alternating with PE can improve survival m SCLC. Between 4190 and S/92, 66 previously untreated patlets with SCLC entered this study. 3 patients were onevaluable. 34 were limited disease (LD), 29 extensive disease (ED) ; 53 were males, 10 females ; 6 were PS 0, 39 PS 1, 11 PS 2, 7 PS 3. The median age was 64 (range 42-75). Patients were initially treated with CAVE (cyclphosphamide 750mg/m* dl , adriamycin 40mglm’ dl, vincristine Zmg/body dl, etoposide IOOmglm d1,2,3)

followed by PE (cisplatinlOOmg/m~ dl, etoposide IOOmglm’ d1,2,3). These regimen were given every 4 weeks for 6 courses. Patients with LD who responded

to chemotherapy received radiation therapy (ZOOcGy, Wweek, total dose 5OGy)

starting 2 weeks after CAVE and PE. Patients with ED were treated with chemotherapy alone. 104 courses of chemotherapy have been administered for LD

and 114 courses for ED. Overall response was 66% with a 6% CR : 65% with a

12% CR for LD and 69% with no CR for ED. The overall median survival time (MST) was 46 weeks with 2-year survwal25%. The MST and 2-year swvival were

50 weeks and 35% for LD and 37 weeks and 10% for ED, respectively. The best 2-year wvival of 57% was obtained in responders (CR+PR) with LD. There were

no deaths due to this treatment. In conclusion, this treatment modality is well tolerated by the patients and

appears to improve long-term survival in SCLC

DOSE ESCALATION STUDY OF CAREOF’LATIN (CBDCA) AND ETOPOSIDE (VP-16) WITH G-CSF IN SMALL CELL LUNG CANCER (SCLC). N. Katakami’. M. Okazaki’, Y. Ariyoshi. H. Ikegami. K. Furuse. M. Fukuoka and West Japan Lung Cancer Study Group. ‘Kobe City Genral Hospital. Kobe, Japan.

We have conducted a phase I-II trial to determine the maximum tolerated dose (MTD) of CBDCA with a fixed dose of VP-16 and G- CSF. Treatment consisted of starting dose oi CBDCA 400 mg/m’ (iv, day 1). VP-16 100 mg/m’ (iv, dayl-3) and G-CSF 2~ g/kg(subcutaneously, day 4-17), every 4 weeks for 4 cycles. The dose of CBDCA was escalated in increments of 50 mg/m’ until grade 4 toxicity on the ECOG scale developed in two-third or more of the patients (pts).

Between Auq. 1991 and Mar. 1993. 75 previouslv untreated pts with pathologicaly comfirmed SCLC were entered in the tr’lal. Seventv one ots were eliaible and 70 ots were evaluable for respon&Cha&teristics of?he 71 pts were’: median age 63 yrs. (49- 79). 58 males/13 females, 45 pts had limited disease and 26 pts extensive disease. Hematological toxicities. complete response rate (CR) and response rate (RR) at each step are as follows:

Step CBDCA No. of Grade 4 Grade 4 CR RR mglm’ pts thrombocytopenia leukopenia % %

(70 ~70 age%70 age170 (70 >70 : 450 400 5 10 8 1 0 0 0

.: 4 4 : 0

: 0 22 83 83

: 500 550 9 12 5 3 29 25 64 92 5 600 9 4 1 25 88 6 7

650 9 700 3

3 j

a i

X7 8B __ -_ 0 67

There were 16 complete responses (23%) and 41 partial responses (58%). The maior dose Ilmiting toxicity was thrombooytopenia. The MTD of CBDCA was reached at a dose of 700 mg/m2 in patients with less than 70-year-old. We conclude that the dose of CBDCA could be escalated salefy until 650 mg/m2 with fixed dose of VP-16 and G-CSF as bone marrow rescue.

385

ANJXOAGULANTS IN SMALL CELL LUNG CAN= (SCLC): A RANINMIZED CLJh’ICALs TRIAL COMPARING FM! WEEKS OF HEFARIN AT CURATIVE DOSAGE vs FIVE MONTHS OF LOW MOLECULAR WEIGHT HEPARIN AT m DOSAGE B. L&em’, Ct. Chastaq, L Jeamin, P. Foacher, L ‘fldbavilk, M. Zasgel, Ph. D&vat, ML QaiiquereI, D. Coetmeur, F. Boita and the “Petitea Cellaks” Group. *HSpitaJ St Antoine. 75012 Park, Fmce.

~wasthcfirsttoindicatcthebmefitofwarfsrinIwein~L(Canar, 1984.53 : 2046). The “Petitea Celh&s” Group tits@ a&died aspiria as a platelet antiagregaat, bat the results were negative (Caacer, 1993.71: 1741). Ihe next eialsbowedabencfitfornspohsesndsurvivatfromsubar~~hepninat curative dmage only in limited diseaws (Lua8 Caaces, 1991.7-suppl: 129). So, iaMay1988,westartedaakt comparitlg 5 weeks of aubcutanmus heparin at curative~2or3~~vcrsus5monthsoflavmolecufsrweight (ulnn?heparinatpreventivedcsagt1wday.379~tswueiadaded(hst lndpstonfebrtury,1W1993)~darcreanalyzedatther~dsrcApril,lst. 1993.310 deaths were recmdad. Eigllty three patkw (22 %) had liiited forms with faders of poor pqaosk. The mutts are ,swmmbd ia the table :

Number Compkte Medkn OfPts response survival

rate (%) (days) Curative haparia 186 22 272

Re-ventive LMW hqtaria 193 22 269

No dierace was obaewed in overaII survival @ - 0.84,2 sided Iograak test). It may be explained by the poor outcome of these patients bat no more difference appearedintbesubgroupofthe84fhaitedfmmp(mrdlaos~ivpl:311~s347 days, p = 0.95). It Ls hnportant to observe that wmpwingowhlsttwo&iaIsfor curative beparia, median sunivsls had dwwed fmm 317 to 272 &ys ttsduciag two differal samplings. In these pAen& a short term curative dosage appears equivalent to a five months preventive dosage.