A phase I study of S-1 and irinotecan combination therapy in previously treated advanced non-small cell lung cancer patients

This phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment. Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m(2) (level 1), 80 mg/m(2) (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m(2), 100 mg/day for BSA 1.25-1.5 m(2), and 120 mg/day for BSA more than 1.5 m(2) on days 1-14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade a parts per thousand yen3 neutropenia with fever over 38A degrees C, grade a parts per thousand yen3 thrombocytopenia, or grade a parts per thousand yen3 major nonhematological toxicities. Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose. The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m(2) combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.