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ORAL ETOPOSIDE (VP-16) AND IV CARBOPLATIN AS FIRST LINE CHEMOTHERAPY IN SMALL CELL LUNG CANCER ST PIERCE, TA TIPTON, WJ JOHN. Division of Hematology & Oncology, Department of Internal Medicine, University of Kentucky Medical Center and Markey Cancer Center, Lexington, KY, USA, 40536.

In an attempt to develop an effective outpatient treatment for small cell lung cancer which preserves quality of life, a phase II trial of oral etoposide and IV carboplatin was initiated. Oral etoposide and IV carboplatin have single agent activity in small call lung cancer. Carboplatin has synergy with VP-16 in pre-clinical studies. Carboplatin and etoposide were given at 300 mg/m2 IV day 1 and SSmg/m2 p.o. day l-10 of every 28 day cycle, respectively. Twenty- three patients, 9 limited, and 14 extensive disease have been treated. Nineteen patients were assessable for response and toxicity with a median follow-up of 67 weeks. There were 8 partial responses (400/o) and 1 complete response (5%) for an overall response rate of 45% (9/19). Limited response was 63% (S/8) while extensive disease response was 36% (4/l 1). The overall median survival was 28+ weeks with limited of 40+ weeks and extensive disease of l9+ weeks. The median progression-free survival was 25 weeks for limited, and lS+ weeks for extensive disease. There has been one treatment related death due to neutropenia and sepsis (5%). Grade 3 or 4 toxicity was limited to myelosuppression with 3 (16%) of patients experiencing neutropenia and 3 (16%) thrombocytopenia.

This regimen appears to be reasonably safe and well tolerated with response rates somewhat lower but with comparable survival to similar protocols.

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FINAL DOSE INTENSITY (FDI) CORRELATES WITH CHEMOTHERAPY OUTCOME IN SCLC Van Meerbeeck, J.P., Verresen, D., Vermeire, P.A., Dept. Resp. Med., Universi$_Hospital Antwerp, Belgium.

Unlike in most studies on dose intensity in SCLC, we calculated the effectively administered dose intensity (DI) in 25 patients treated between 1988-91 with doxorubicin (45 mg/m2, dl), cyclophosphamide (1 g/m2, dl) and etoposide (100 mg/m2, dl-3). We therefore used Wampler’s et al. formula for final dose intensity (FDI) (Cancer Chemother. Pharmacol., 1992, 30, 199) on the data of 22 men, 3 female, median age 60 y (43-75), of whom 10 were LD, 15 ED, 48% obtained a CR and 36% a PR. Spearman rank correlation showed a p CO.01 significant difference in FDI between the CR group (0.93% f 0.131, PR group (0.80% f 0.15) and the others (0.50% f 0.09). There was a r=0.56 correlation between FDI and survival. Multiple linear regression analysis disclosed that FDI was an indepen- dent prognostic factor for survival (8 0.63; p < 0.01) besides disease extent and age. Median survival of patients with FDI zc 0.75% (5.7 m) was signficantly different from pa- tients with FDI > 0.75% (I 1.3 m) (p~O.05). We conclude that FDI should be used instead of protocollar dose intensity for studies on the effect of dose intensity on outcome in SCLC.

A PHASE II STUDY OF IRINOTECAN COMBINED WITH CISPLATIN IN PATIENTS WITH SMALL-CELL LUNG CANCER Kudoh, St), Kurihara, N.t), Fukuoka, M.2) Fujiwara, Y.2) Furuse, K.2) Ikegami, H.2) Ariyoshi, Y.2) 1)Osaka City University, Osaka, Japan, and 2)West Japan Lung Cancer Treatment Group,

lrinotecan (CPT-1 1) a water-soluble derivative of camptothecln, is a topoisomeraae I inhibitor, which is effective as monotherapy against small-cell lung cancer (SCLC) (ASCO, 1991,#822). A phase II study of combined CPT-11 and cisplatin (CDDP) therapy was conducted to evaluate the efficacy and toxicity in patients (pts) with previously untreated SCLC. Based on results of a phase I study (AACR, 1993, X1227), CPT-11 was administered intravenously at a dose of 80 mglm2 on days 1, 8, and 15 in combination with CDDP (60 mglm2) on day 1 every 28 days. However the dose of CPT-11 was reduced to 60 mg/m2 because severe toxicities were observed in initial 10 pts. Four courses of chemotherapy followed by thoracic irradiation were given to LD pts and six courses to ED pts. Registration was completed for 75 pts. To date, 34 pts have been evaluated. The pts characteristics Included male/female : 26/8, median age of 64 years, LD/ED: 19/15, and PS O-1/2 : 28/E. There were 32 evaluable pts for response. The overall response rate was 78% (25/32), while It was 78% for LD and 79% for ED. Complete response (CR) was achieved in four LD pts (22%) and three ED pts (21%). The major toxicities (2 ECCG grade 3, n=34) were leukopenia (47%) anemia (38%) thrombocytepenia (15%). diarrhea (21%) nausea (32%) and vomiting (9%).

Our interim results suggest that this combination is active against SCLC.

397

CISPLATIN + ETOPOSIDE (CE) VERSUS CE ALTERNATED WITH CYCLOPHOSPHAMIDE + EPIRUBICIN + TENIPOSIDE (EVE) IN SMALL CELL LUNG CANCER (SCLC). D. Galetta. E. Durini. E. Maiello. F. Giotta, C. Del Casale, S. Romito, G. Colucci. - O"cology Institute Bari and G.Panico Hospital Tricase (LE). ITALY.

TO compare the efficacy of CE versus an alternating schedule (CE-EVE), patients with histologically confirmed SCLC were randomized to receive, every three weeks: C 100 mg/mq dl and E 80 w/mq dl-3 (Arm A), or CE alternated with cyclophosphamide 750 w/mq dl, epirubicin 60 mg/mq dl. teniposide 60 w/mq d1,2 (Arm 8). Thirty-five patients entered in the study. At present, 26 (A-lS;B-11) pts are evaluable for response. The main characteristics are as follows: sex (M/F) 25/l; median age 61 yrs (range 44-70); median Karnofsky PS 80; limited disease (LD) 8 pts (A-5;B-3); extended disease (ED) 18 pts (A-lB;B-8); site of disease: lung 26. lymphnode 19. liver 8, bone 7, adrenals 4. skin 3. We observed 5 (A-4PR; B-1CR) and 14 (A-2CR+6PR; B-3CR+3PR) objective responses in LD and ED, respectively. Overall response rate “a5 80% in arm A and 64% in arm B. Grade 3-4 toxicities (WHO criteria) observed in the 35 entered pts were as follows (A/B): anemia 5 Pts (4/l). leukopenia 1 (l/0). nausea/vomiting 7 (S/2). loss of hair (2/7). One death related to treatment was observed in arm A due to a grade 4 renal toxicity. Our preliminary results showed that the alternated regimen did not seem to improve response rate.