Background: Based on promising data with weekly high-dose (HD) continuous 5-fluorouracil (5-FU) and folinic acid (FA) in patients with gastric carcinoma (GC) refractory to 5-FU bolus application, we investigated a weekly combination of HD-5-FU/FA with cisplatin (C) and epirubicin (E) as first-line treatment in patients with advanced GC. Methods: 27 patients with locally advanced or metastatic GC were treated with up to three 6-week courses of FUFACE (5-FU, FA, CE). Chemotherapy was planned preoperatively in localized tumors. Results: Toxicity was usually moderate, but response-independent weight loss and lethargy caused protocol deviations in 30% of the patients. Response rates were 50% and 91% in metastatic and locally advanced tumors, respectively. All patients with localized disease had complete tumor resection at subsequent surgery. Median survival was 20+ months in this patient group. Conclusions: This weekly chemotherapy regimen seems to be very effective in advanced GC. The high response rate and resection rate in locally advanced tumors favours this regimen particularly in the preoperative setting.