Dose escalation study of amrubicin in combination with fixed-dose irinotecan in patients with extensive small-cell lung cancer

Background: The combination of amrubicin (Am) and irinotecan (CPT) shows appreciable activity against small-cell lung cancer (SCLC) in vitro. Patients and Methods: We conducted a dose escalation study of Am in combination with CPT to determine the qualitative and quantitative toxicities and efficacy against extensive (ED) SCLC. Results: Thirteen previously untreated patients with ED-SCLC were treated with CPT at 60 mg/m(2) on day 1 and dose-escalated Am on days 1-3 with prophylactic granulocyte colony-stimulating factor subcutaneously on days 5-9 every 2-3 weeks. At level 3 (40 mg/m(2)/day Am), 3 of 4 registered patients experienced dose-limiting toxicity such as grade 4 neutropenic fever, and therefore, this was defined as the maximum tolerated dose. A total of 31 courses was administered at dose level 2 (35 mg/m(2)/day) in 6 patients, and grade 4 neutropenia was observed during 5 courses (16.1%). Non-hematological toxicities, except 1 course of grade 3 transfusion of red blood cells and 1 course of grade 3 transaminase elevation, were mild. Thus, dose level 2 of Am was recommended for further study. One patient achieved complete remission and 12 achieved partial remission, and the overall response rate was 100%. The median survival time was 17.4 months, and the 1-year survival rate was 76.9%. Conclusions: CPT at 60 mg/m(2) on day 1 and Am at 35 mg/m(2)/day on days 1-3 with granulocyte colony-stimulating factor support every 3 weeks is recommended for Japanese patients with ED-SCLC. Copyright (c) 2008 S. Karger AG, Basel.