708

183

709

RAPIDLY ALTERNATING HYPERFRACTIONATED ACCELERATED RADIOTHERAPY (AHR) AND COMBINATION CHEMOTHERAPY (CT) IN STAGE III NON-SMALL CELL LUNG CANCER (NSCLC) : RESULTS OF GOTHA I AND II. R.O. Hirimanoff’. P. Albe&. A. Roth’. D. Nerd. G. Michel’. 8. Mermillod2. H. Bolla’. Grwpe d’0ncologie l&racique Alpine, University of Lausanne'. Geneva' and Grenobl? (Switze~land’~‘. Francd)

m : To evaluate schedules of rapidly alternating AHR and combination CT, patients with stage III NSCLC were entered in two consecutive phase II studies : GOTHA I (GI) and GOTHA II (GII). I&I&& : In GI, 3 cycles of cisplatin (P), 60mg/m2 d 1, Mitomydn, 8mg/m2 d 1 and Viidesin 3mg/m2 d 1 and 8, during weeks 1, 5 and 9, were alternated with 2 courses of AHR 30 and 33 Gy at 1.5 Gy bid (total 63 Gy) during weeks 2, 3 and 6,7. In GII, P 70mg/m2 dl and Viiblastin 8mg/m2 d 1 and 8, were given on weeks 1,5,9,13,17 and 21 and AHR (same as above : 63 Gy) during weeks 2,3 and 6,7. Patients less than 70 y, with PS O-l, FEV, > 1.5 1 and normal renal and liver function were eligible. J&& : One hundred and thirty four patients (GI : 66, Feb. 1986 - Dec. 1988, GII: 68, Jan. 1989 _ Dec. 1991) were included. There were 118 males (56 and 62), 82 S.C.C. (45 and 37), 28 adeno (16 and 12), 16 large c. (2 and 14), 55 stage IIIA (31 and 24) and 76 IIIB (33 and 43). In GI and GII, grade 3-4 toxicities were : leucopenia 43% and 36%, thrombocytopenia : 12% and 7%, nausea : 11% and 21%, and mucositis : 9% and 21%, respectively. Two patients died shortly after treatment from acute hemoptysis. To date, 104 patients relapsed: Gl:5.5/66 and G11:49/68, locally in 24% and 41%, distantly in 49% and 27%, and both in 15% and 16%, respectively. For Gl, with a minimum follow-up of 5 years, median survival (MS) was 15.7 months (CI : 10.7-19.0) with a 2,3 and 5 yew survival of 26%, 18% and 14%. For GII with a minimum follow-up of 2 years, MS was 13.3 mo. (CI 10.1-17.8) with 2 and 3 year swvivaI of 26% and 16%, respectively. Conclusion : Based on our experience in 134 patients, rapidly alternating AHR and platin-based CT is feasible with acceptable. toxicity. We are now comparing this programme to AHR alone in an on-going phase III randomized trial (GOTHA III).

Concurrent cisplatin-vindesine and bifractionated thoracic radiotherapy (RT) in locally advanced non small cell lung center ILANSCLC). R. Arriagada, T. Le Chevalier, J J Bretel, B Pellae-Cosset, P. Ruffie. lnstitut Gustave-Roussy, 94805 Villejuif, France.

Local control is a major problem in LANSCLC. The main objective of this phase II trial was to test the feasibility of a combined concurrent therapeutic approach in an attempt to improve local control. Inclusion criteria were: age 70 or less, KI > 60%, no previous treatment, no distant metastases. The treatment schedule consisted of: bifractionated RT (60 Gy/4

1 fractions/6 weeks, 1.25 Gy per

fraction), cisplatin 6 mg/m each day of RT, vindesine 2.5 mglm2 weekly during RT. After a 3-week rest period, two full cycles of cisplat? (120 mg/m2 week 10 and 14) and vindesine (2.5 mg/m week 1 l-13) were given. Treatment evaluation (thoracic CT scan, fiberoptic bronchoscopy, bronchial biopsies) was performed 3 months after completion of RT. Failure rates were estimated by a competing risk approach. From December 1989 to December 1992, 34 patients were included. Population characteristics include: 28 men, mean age: 56 years, mean KI: 88%.

Results: CR: 18/34 (53%). Local control rates at 1 and 3 years were 50% and 46%. Distant metastases rates at 1 and 3 years were 27% and 31% respectively. Overall survival at 1, 2 and 3 years, 52%, 33% and 13%, respectively. Lethal toxicity developed in two patients (bone marrow aplasia and renal failure). In conclusion, this phase II trial confirms the feasibility of this type of approach. It suggests the possibility of improvement in local control as compared to conventional approaches. Radiation dose escalation remains possible within the analyzed schedule.

711

PBASE II STUDY OF CONCURRPNT WHOLE BR*LIN RADIOTBERAPY (WBRT) P CHEMOTHERAPY (CT) COMBINED WITH CISPLATIN CC). VINDESINE (V). 6r HITOIYCIN (I) FOR NON-SHALL CBLL LUNG CANCER (NCSLC) WITH BRAIN MBTASTASIS. T. Kamimori, K. Furuse. M. Kawahara, N. Kodama. K. Kubota, M. ooawara. T. Okada and Y. Kawaguchi, National Kinki Central tiospital for Chest Disease, Sakal, Osaka 591. Japan Patients lpts) with brain metastasis from NSCX are most commonly treated with WBRT & admlnistration of corticosteroids. Response to WBRT L" spite of cllnlcal improvement in 50% or more of the treated pts :s limited to a short period of 4 months or less. Recect sttidles suggest that effect of CT o" the tumors may be more dewzndenc on the chemosensitlvitv of the tumor than on the ability of the drug to cross ar A"tacr blood-brain barrier. The", the comblnatio" of WBRT & CT could result in additive or synergistic cytotoxlc effects. Purpose: to increase the neuroiogic response & to improve the quality of life (QOL) 1" the pts of NSCLC with brain metastasis, we used concurrent WBRT & CVM. Pts & Methods: eligibility criteria included brain metastasis, 5 75 years & PS c 4. Treatment consisted of C 80 mg/m' intravenously (IV) on day 1 & 29, V 3 w/m' I" on day 1.8 & 29, 36, M 8 mglm' on day 1 & 29. with concurrent WBRT (40 Gy :n 20 fractions). Results: median

25 pts were eligible: 13 male & 12 female; age 59 Irange; 39.74); PS l/2/3=5/12/8;

squamous/ade"ocarcinoma/large cell=4/3/18; 19 no prior theraw & 5 no svmotoms of brain metastasis. Of the eligiiie 25 pts, 2-w-s had a complete response (CR), 20 a partial response (PR), 3 no change (NC), 4 overall response rate was 84% against bral" lesions. The median duration of response & survival is i..r lrancie. I.5 months to :7.5 months)-& 7+ months, respectively. Ail 19 pts who had neurological symptoms before tr~atmert had neurologlc respon.SE?. and NF (RTOG) of these pis was improved more than one score. I" PS after the treatment, 11 pts had imxxovement of PS of one score. 12 Dts had no chanoe and 2 pti had worse than one score. No treatment related-death & no acute toxicities to central nervous system. In conclus~o": concurrent WBRT & C"M induced a high overall I-eSpCl*St? rate Of brain metastasis & significant lmpro"eme"t Of "eurologlcal symptoms & OOL.