Phase I study of S-1 combined with irinotecan (CPT-11) in patients with advanced colorectal cancer.

ABSTRACT

PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 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 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.