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

Cancer Chemother Pharmacol. 2009 Jan;63(2):213-8. doi: 10.1007/s00280-008-0728-4. Epub 2008 Mar 15.

Abstract

Purpose: To determine the maximum-tolerated dose (MTD) of a 24-h 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 and 30 mg/m(2), respectively. The dose of 5-FU was increased from a starting dose of 1,000 mg/m(2) to the MTD.

Results: A total of 53 cycles of chemotherapy were administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m(2). All 21 patients were assessed for toxicity and 19 patients (90%) were evaluated for response. Both grade 3-4 hematologic and non-hematologic toxicities occurred in less than 10% of patients and there were no treatment-related deaths. Among the 19 patients, we observed 1 complete and 4 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 4-week intervals appears feasible for advanced gastric cancer with a favorable toxicity profile. The recommended doses are 33.3 mg/m(2) of docetaxel, 30 mg/m(2) of cisplatin and 1,500 mg/m(2) of a 24-h continuous intravenous infusion of 5-FU. The response of this weekly regimen in our study was favorable and deserved further investigation in a phase II trial.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use
  • Humans
  • Infusions, Intravenous
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / pathology
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Taxoids / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Taxoids
  • Docetaxel
  • Cisplatin
  • Fluorouracil