A phase I study of combination therapy with S-1 and irinotecan (CPT-11) in patients with advanced colorectal cancer

Purpose  The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer. Methods  S-1 was administered orally at 80 mg/m² per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m² per day, stepping up to 100, 120 or 150 mg/m² per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed. Results  A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m², because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m². Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0–14.0 months). Conclusion  A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.