The purpose of this study was to determine the optimal dose of oxaliplatin, when combined with a fixed dose of S-1 (40 mg/m twice daily on days 1-14) on a 3-week schedule, for patients with advanced and/or metastatic colorectal cancer. Patients were required to have a histologically proven advanced or metastatic colorectal cancer for which they had received no previous chemotherapy. Oxaliplatin was administered intravenously on day 1 every 3 weeks. Patients were divided into two groups to receive two doses of oxaliplatin - 100 mg/m or 130 mg/m. Ten patients were enrolled in the study between March 2006 and July 2006, and were followed up until 50% of the patients progressed. All patients were evaluated for chemotherapy-related toxicity. The maximum tolerated dose was not reached during the first course. One of six patients experienced grade 3 thrombocytopenia at dose level 2 of oxaliplatin. Nonhematological toxicity was mild and tolerable. During the full course of treatment, complete response was achieved in two of the nine evaluated patients and partial response was achieved in one patient. The remaining six patients achieved stable disease during first two courses of therapy, and four patients remained stable at the time of the last follow-up. The median time to progression-free survival was 8.3 months. When combined with a fixed dose of S-1 80 mg/m, oxaliplatin administered at a dose of 130 mg/m is tolerable and recommended for phase II study.