RANDOMIZED STUDY OF NAVELBINE(R) AND CISP LATIN VERSUS VINDESINE AND CISPLATIN VERSUS NAVELBINE(R) ALONE IN 612 PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG-CANCER (NSCLC)

The combination of vindesine and cisplatin is considered a reference r egimen in advanced NSCLC which has yielded a significant improvement i n the duration of survival. A phase II study of a new semi-synthetic v inca alkaloid, Navelbine(R), reported an unusually high 29% response r ate in stage III-IV NSCLC and a phase I-II study established the feasi bility of the combination of Navelbine(R) and cisplatin. We, therefore , designed a prospective randomized trial to compare Navelbine(R) and cisplatin (NVB-P) to vindesine and cisplatin (VDS-P) and to evaluate w hether the best of these regimens affords a survival benefit compared to Navelbine(R) alone (NVB), an outpatient regimen. Forty-five centers included 612 patients in this study: 206 in NVB-P, 200 in VDS-P and 2 06 in NVB. Navelbine(R) was given at a dose of 30 mg/m(2) weekly, cisp latin at 120 mg/m(2) on day I, day 29 and then every 6 weeks and vinde sine at 3 mg/m2 weekly for 6 weeks and then every other week. Treatmen t was continued until progression or toxicity. Patients' characteristi cs were similar in the three groups with 59% of patients presenting wi th metastatic disease. An objective response rate was observed in 30 % of patients in NVB-P versus 19 Cio in VDS-P (P = .02) and 14 % in NVB (P <.001). The median duration of survival was 40 weeks in NVB-P comp ared to 32 weeks in VDS-P and 31 weeks in NVB. The comparison of survi val between the three groups demonstrated an advantage for NVB-P compa red to VDS-P (P = .04) and NVB (P = .02). Neutropenia was significantl y higher in the NVB-P group (P < .001) and neurotoxicity more frequent with VDS-P (P < .004). Since our results have demonstrated that NVB-P yields a longer survival duration and a higher response rate than VDS -P or NVB alone, with acceptable toxicity this combination should be c onsidered a reference regimen in advanced NSCLC.