Phase I Evaluation of Continuous 5-Fluorouracil Infusion Followed by Weekly Paclitaxel in Patients with Advanced or Recurrent Gastric Cancer

Abstract

Objective: We conducted a phase I trial of escalating doses of weekly paclitaxel (Taxol) in combinationwith a fixed systemicadministration of 5-fluorouracil (5-FU) in patientswith advanced or metastatic gastric cancer. Methods: Patients with advanced or recurrent gastric cancer were treated with escalating doses of weekly paclitaxel as a 60 min intravenous (i.v.) infusion, along with a fixed dose of continuous 5-FU infused over 5 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel. Results: Eighteen patients received combination therapy at four dose levels of weekly Taxol, ranging from 60 to 90 mg/m2/week. Dose-limiting toxicities>grade 3 were observed at the 90 mg/m2/week dose level. Toxicities included anemia, neutropenia, thrombocytopenia, nausea and alopecia. Two episodes of grade 4 neutropenia occurred in two of the three patients receiving this dose. At each dose level, pharmacological studies documented the persistence of significant serum paclitaxel levels over 24 h after drug administration. The maximum tolerated dose (MTD) for this regimen was 90 mg/m2/week of paclitaxel for 3 weeks plus 600 mg/m2/day of continuous 5-FU for 5 days