Phase II Study of Irinotecan plus S-1 Combination for Previously Untreated Advanced Non-Small Cell Lung Cancer: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0601

Objective: Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC. Methods: Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m2, days 1 and 15) and oral S-1 (80 mg/m2, days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival (OS), progression-free survival (PFS), and safety. Results: A total of 112 cycles was administered to 40 patients (median, 3 cycles; range 1-6 cycles). Twelve patients showed partial response (PR) and 17 patients exhibited stable disease (SD), representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 months and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common non-hematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055). Conclusion: The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.