To evaluate the activity and safety of a combination chemotherapy with epirubicin, cisplatin, and a protracted venous infusion of 5-fluorouracil (ECF) in unresectable or metastatic gastric cancer, a phase II study was performed. Thirty-five chemotherapy-naive patients were given ECF. Epirubicin (50 mg/m intravenous, IV) and cisplatin (60 mg/m IV) were administered every three weeks during a continuous intravenous infusion of 5-fluorouracil (250 mg/m /day) using infusion pump. One complete response and 19 partial responses (response rate=62%) were achieved. Eight patients remained stable, whereas in four patients the disease progressed. The median duration of response was 22 weeks (95% confidence interval, 18-27 weeks). The median survival for all patients was 10 months (95% confidence interval, 6-14 months), with a 1-yr survival rate of 40%. A total of 184 cycles of chemotherapy were administered. Grade 3 or 4 emesis occurred in 3%, mucositis in 2%, anemia in 10%, and leukopenia in 3% of the cycles. Central venous catheter complications that required line removal occurred in 37% (n=13) of the patients. No patient died of toxicity. Overall, the ECF regimen showed high anti-tumor activity with a tolerable toxicity pattern.