Fractionated administration of irinotecan and cisplatin for treatment of extensive-disease small-cell lung cancer: A phase II study

Background: A combination of irinotecan (CPT-11) and cisplatin (CDDP) was shown to be effective for extensive-disease small-cell lung cancer (ED-SCLC). To take maximum advantage of the synergistic effect between CPT-11 and CDDP, we designed a fractionated administration schedule. Patients and Methods: Between August 1995 and September 1998, 15 previously untreated patients with ED-SCLC were enrolled. Both CPT-11 at a dose of 50 mg/m² and CDDP at a dose of 60 mg/m² were given on days 1 and 8, and repeated every 4 weeks up to four cycles. Results: Fifteen patients were assessed for response and survival, and fourteen for toxicity. Although twelve patients (80.0%; 95% confidence interval, 51.9-95.7) achieved an objective response, complete response (CR) was not obtained. The median survival time and the actual 1-year survival rate were 9.4 months and 40.0%, respectively. Grade 3 or 4 leukopenia, neutropenia and diarrhea occurred in 71.4%, 100% and 14.3% of the patients, respectively. Enrollment into this study was stopped because CR, which was the primary endpoint, was not obtained in the consecutive 15 patients and the survival appeared to be inferior to the previous multi-institutional study (Kudoh et al, Clin Oncol 16: 1068-1074, 1998). The projected dose intensity in the present study was lower in CPT-11 and higher in CDDP compared to that in the previous report. Conclusion: These results suggest that the dose intensity of CPT-11 may have a major role on the activity of SCLC in this combination.