PURPOSE: There is no effective treatment for patients with advanced gastric cancer having failed to respond to first line chemotherapy. The aim of this study was to evaluate the therapeutic activity, and safety, of a FEP regimen in patients with a recurrence of, or metastatic, gastric cancer that had been unresponsive to primary chemotherapy. MATERIALS AND METHODS: Recurred or metastatic gastric cancer patients that did not respond to a 5-fluorouracil based regimen were entered into this trial. The patients were treated with FEP (5-FU, etoposide and cisplatin) as salvage chemotherapy. The treatment regimen was 5-FU (900 mg/m2/day) by continuous infusion for 3 days, etoposide (90 mg/m2/day) on days 1, 2 and 3, and cisplatin (60 mg/m2/day) on day 2. This treatment was repeated every 3 weeks. RESULTS: Between December 1997 and October 2001, 28 patients were enrolled to the study. The response rate was 32.1% (95% CI 15.5~57.8%). The median times to progression and survival duration were 23~33 weeks, respectively. Among a total of 187 cycles of chemotherapy, the grade 3 and 4 hematological toxicities were leukopenia (6.4%), thrombocytopenia (1.6%), and grade 3 non-hematological side effects of nausea/vomiting (17.9%). CONCLUSION: FEP combination chemotherapy seems to be an effective treatment regimen for gastric cancer as salvage chemotherapy. To confirm these results, large scale of clinical trials will be required.