Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer

To determine a standard combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC), we conducted a phase III trial of irinotecan (CPT-II) to test the hypotheses that CPT-II +cisplatin is superior to cisplatin+vindesine and that CPTI II monotherapy is not inferior to cisplatin+vindesine. A total of 398 patients with previously untreated NSCLC were randomised to receive cisplatin+CPT-II (CPT-P), cisplatin+vindesine (VDS-P) or CPT-II alone (CPT). In the CPT-P arm, CPT-II 60 mg m(-2) was administered on days 1, 8 and 15, and cisplatin 80 mg m(-2) was administered on day 1, In the VDS-P arm, cisplatin 80 mg m-2 was administered on day 1, and vindesine 3 mg m-2 was administered on days 1, 8 and 15. In the CPT arm, CPT-II 100 mg m(-2) was administered on days 1, 8 and 15. The median survival time was 50.0 weeks for patients on CPT-P, 45.6 weeks for those on VDS-P and 46.0 weeks for those on CPT (P = 0.115, CPT-P vs VDS-P; P = 0.089, CPT vs VIDS-P), and the hazard ratio was 0.85 (95% confidence interval (Cl): 0.65-1.11) for CPT-P vs VDS-P and 0.83 (0.64-1.09) for CPT vs VDS-P, The response rate was 43.7% for patients on CPT-P, 31.7% for those on VDS-P and 20.5% for those on CPT. Major adverse reactions were grade 4 neutropenia observed in 37, 54 and 8% of the patients on CPT-P, VDS-P and CPT, respectively; and grades 3 and 4 diarrhoea observed in 12, 3 and 15% of the patients, respectively. CPT-P therapy produces comparable survival to VDS-P in patients with advanced NSCLC. CPT-II monotherapy is not inferior to VDS-P in terms of survival. The CPT-II-containing regimen is one of the most efficacious and well tolerated in the treatment of advanced NSCLC. (C) 2003 Cancer Research UK.