Phase I dose-escalating study of 24-hour continuous infusion 5-fluorouracil in combination with weekly docetaxel and cisplatin in patients with advanced gastric cancer

Abstract

15652 Background: In a phase III study (V325), a combination of Docetaxel, Cisplatin and 5-FU (DCF) showed higher efficacy compared to the control arm of the CF regimen, but also higher side effects. We conducted this study to determine the maximum tolerated dose (MTD) of a 24-hour continuous infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed weekly dose of Docetaxel and Cisplatin in patients with advanced gastric cancer. Methods: Patients with advanced gastric adenocarcinoma (n=21) received a weekly regimen of Docetaxel, Cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4 weeks. The doses of Docetaxel and Cisplatin were fixed at 33.3 mg/m2 and 30 mg/m2, respectively. The dose of 5-FU was increased from a starting dose of 1000 mg/m2 to the MTD. Results: A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1750 mg/m2. All patients were assessed for toxicity and 19 (90%) were evaluated. Both grade 3–4 hematologic and non-hematologic toxicities occurred in less than 10% and there were no treatment-related deaths. Among the 19 patients, we observed one complete and four partial responses for an overall response rate of 26% (95% CI: 6–46%). This rate increased to 39% (95% CI: 12- 66%) in 13 chemotherapy-naïve patients. Conclusions: A consecutive weekly DCF regimen at four-week intervals appears effective for advanced gastric cancer and has a tolerable toxicity profile. For a further phase II study, the recommended doses are 33.3 mg/m2 of Docetaxel, 30 mg/m2 of Cisplatin and 1500 mg/m2 of a 24-hour continuous intravenous infusion of 5-FU. No significant financial relationships to disclose.