OBJECTIVES: A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer. PATIENTS AND METHODS: Twenty-nine patients with unresectable and/or metastatic gastric cancer were enrolled in the study. Paclitaxel 50 mg/m(2) was administered on days 1 and 8. S-1 was administered orally at 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. The primary endpoint was the response rate. Secondary endpoints were safety and overall survival. RESULTS: The overall response rate in 29 patients was 48.3%, differentiated 36.4% and undifferentiated 55.6%. The median survival time was 13.9 months. Grade 3 or higher toxicity was observed in neutropenia (3.4%), diarrhea (3.4%), bilirubin (3.4%) and neuropathy (3.4%). CONCLUSIONS: Combination chemotherapy of weekly paclitaxel and S-1 demonstrated tolerable toxicity and efficacy. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer. Copyright 2008 S. Karger AG, Basel.