A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer

Background: This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. Patients and methods: Patients were randomly assigned to receive carboplatin area under the curve 5 mg.min/ml either in combination with irinotecan 50 mg/m(2) on days 1, 8, and 15 (IP) or etoposide 140 mg/m(2) on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity. Results: Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm. Conclusion: This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.