MULTICENTER RANDOMIZED TRIAL COMPARING CISPLATIN-MITOMYCIN-VINORELBINE VERSUS CISPLATIN-MITOMYCIN-VINDESINE IN ADVANCED NON-SMALL-CELL LUNG-CANCER

The study was designed to evaluate the value of vinorelbine in a cispl atin-mitomycin-vinca alkaloid regimen for treatment of locally advance d or metastatic non-small cell lung cancer (NSCLC). A group of 227 pat ients with inoperable NSCLC in stage III (58%) or stage IV (42%) were included in this randomized multicenter trial comparing a reference re gimen (VDS group, n = 113) cisplatin (120 mg/m(2) on day 1, day 29 and day 71), mitomycin (8 mg/m(2) on day 1, day 29 and day 71) and vindes ine (3 mg/m(2)/week for 5 weeks and then every 2 weeks up to the 15th week) to a cisplatin-mitomycin-vinorelbine combination (VNB group, n = 114), with cisplatin and mitomycin at the same doses, and vinorelbine 25 mg/m(2)/week for 16 weeks. The objective response rate (evaluated at 17th week) was 17% in the VDS group and 25% in the VNB group (P = 0 .15). Median survival was 33.4 weeks and 34.5 weeks in the VDS and VNB arms, respectively. Overall survival duration was not significantly d ifferent between the two arms (logrank test, P = 0.20) despite a trend to an increased survival in the VNB group. This essentially benefited the patients with stage III disease with a clear-cut lengthening of m edian (45.9 vs. 33.4 weeks) and 1 year survival (44.6% vs. 26.2%, P < 0.05) in favor of the VNB group. Nevertheless, there was no significan t difference in overall survival (logrank, P = 0.13). Survival duratio n of the patients with stage IV disease was comparable in the two arms (logrank test, P = 0.90). Grade 3 or 4 neutropenia was found in 61% a nd 87% of the VDS and VNB groups, respectively (P < 0.01). Grade 2-4 p eripheral neuropathy was observed in 23% of the patients in the VDS gr oup and in 6% of the patients in the VNB group (P < 0.01). Replacement of vindesine by vinorelbine in a cisplatin-mitomycin-vinca alkaloid c hemotherapeutic regimen did not lead to a significant improvement in o bjective response rate or in duration of survival. There was a reducti on in neurotoxicity at the expense of an increased hematologic toxicit y. However, for patients with stage III disease there was an increase in 1 year survival with the vinorelbine combination.