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Combination chemotherapy with continuous 5-fluorouracil (5-FU) and cisplatin in a monthly regimen is one of the standard treatments for advanced gastric carcinoma. This study evaluated the new LV5FU2-P regimen, designed to improve efficacy and tolerance of the 5-FU plus cisplatin combination.Forty-three patients with advanced or metastatic gastroesophageal junction or gastric carcinoma were prospectively included in the study. They were treated every 14 days with cisplatin 50 mg/m2 on day 2 plus folinic acid 200 mg/m2/day as a 2-h intravenous (i.v.) infusion on days 1 and 2, plus bolus 5-FU 400 mg/m2/day on days 1 and 2, plus continuous 5-FU 600 mg/m2/day as a 22-h i.v. infusion on days 1 and 2. Ten patients received a simplified regimen (folinic acid 40 mg/m2 day 1 + bolus 5-FU 400 mg/m2 day 1 + continuous 5-FU 2400 mg/m2 on days 1 and 2 with cisplatin 50 mg/m2 on day 2).All the patients were assessable for response and 42 for toxicity. One patient achieved a complete response and 15 a partial response, for an overall response rate of 37.2% [95% confidence interval (CI) 22.1% to 52.3%]. The median progression-free survival was 7.2 months (95% CI 5.4–10.9) and the overall survival was 13.3 months (95% CI 10.1–16.4). There were no treatment-related deaths. Hematological and gastrointestinal toxicities were the most common severe toxicities.LV5FU2-P is an active and well tolerated regimen in the treatment of advanced gastroesophageal junction or gastric carcinomas. It warrants evaluation comparatively with other active regimens.