A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer.

PURPOSES: To determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer.

METHODS: Oxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1-7, every 2 weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60 mg/m(2); level 2, 85/120/80 mg/m(2); level 3, 85/120/100 mg/m(2); level 4, 85/150/100 mg/m(2); and level 5, 85/180/100 mg/m(2). Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity.

RESULTS: Twenty-four patients were enrolled between October 2012 and February 2014 (median age 59 years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6 %.

CONCLUSIONS: The combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85 mg/m(2) of oxaliplatin, 180 mg/m(2) of irinotecan, and 100 mg/m(2) of S-1 every 2 weeks.