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A phase I–II multicenter trial was conducted to define the maximum tolerated dose (MTD) according to tolerance and toxicity (primary objective), as well as to describe the clinical activity, in terms of response and survival (secondary objectives), of a combination of 5-fluorouracil (5-FU) in protracted continuous intravenous infusion (p.i.v.) with docetaxel and cisplatin for patients with advanced gastric cancer.Patients with measurable unresectable and/or metastatic gastric carcinoma, World Health Organization performance status ≤1, normal hematological and renal functions, adequate hepatic function and not pretreated for advanced disease by chemotherapy, received up to eight cycles of a combination of docetaxel on day 1, cisplatin on day 1 and 5-FU p.i.v. on days 1–14 (TCF) every 3 weeks, which was escalated up to the MTD, defined by the occurrence of dose-limiting toxicity in two patients in one dose level.Fifty-two patients were accrued and treated (43 in the phase I part of the trial and nine additional at the recommended dose level). A median of five cycles/patient was given. The recommended dose of TCF was docetaxel 85 mg/m2 on day 1, cisplatin 75 mg/m2 on day 1 and 5-FU p.i.v. 300 mg/m2/day on days 1–14. Grade ≥3 toxicities were neutropenia 79%, alopecia 46%, fatigue 23%, mucositis 10%, diarrhea 19%, nausea/vomiting 13%, neurological 4% and palmar-plantar 2%. Ten non-fatal febrile neutropenia episodes were recorded in eight patients. There were no treatment-related deaths. Among 41 patients with measurable disease (79%), we observed one complete and 20 partial responses for an overall intent-to-treat response rate of 51% (95% confidence interval 35–67%). Five patients (20%) had stable disease for ≥12 weeks (four cycles). The median overall survival was 9.3 months.5-FU p.i.v. at 300 mg/m2/day for 2 weeks out of three could be safely added to the docetaxel–cisplatin (TC) combination, but the dose of docetaxel had to be reduced to 75 mg/m2 in a subsequent phase II trial. This drug regimen seems to be very active in advanced gastric cancer. Comparison with both TC and ECF in a randomized SAKK trial is ongoing.