Phase I study of irinotecan and S-1 combination therapy in patients with metastatic gastric cancer

Abstract

Irinotecan was given intravenously over the course of 90 min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m² per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100 mg/m² (level 1; n = 3), to 125 mg/m² (level 2; n = 3), and 150 mg/m² (level 3; n = 6). Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m² of irinotecan on day 1 and 80 mg/m² per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response. A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.