A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer

Background: Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP). Patients and methods: The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg . min/ml either in combination with 50 mg/m(2) of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m(2) days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival. Results: Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03). Conclusions: IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.