A phase I trial of S-1 with oxaliplatin in patients with relapsed and metastatic colorectal cancer

S-1 showed clinical activity in colorectal cancer, and the preclinical data of S-1 with oxaliplatin showed synergistic activity in an animal model. This phase I study was conducted to determine the maximum tolerated dose of S-1 with oxaliplatin and to define its recommended dose for the subsequent phase II study.Patients with untreated colorectal adenocarcinoma were eligible in this study if they had measurable lesions. S-1 was administered on days 1-14, with doses starting from 60 mg/m2 per day and escalating by 10 mg/m2 at each dose level. Oxaliplatin was given at the fixed dose of 130 mg/m2, through 2-h i.v. infusion on day 1. The treatment was repeated every 3 weeks.A total of 27 patients received six different S-1 dose levels. The dose-limiting toxicities (DLTs) were neutropenia, diarrhea, and vomiting. At dose level 5 (100 mg/m2), two patients experienced DLTs, while none of the third cohorts did. At dose level 6 (110 mg/m2), two patients experienced DLTs, and one of them died from treatment-related toxicity. The accrual was then stopped.The recommended dose is S-1 100 mg/m2 on days 1-14, with 130 mg/m2 oxaliplatin on day 1, every 3 weeks. This regimen is proposed for the phase II study.