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ONCOLOGY Vol 14 No 10

In the United States and Europe, the combination of oral UFT plus leucovorin has been reported to produce objective responses and survival rates similar to those achieved with standard intravenous 5-fluorouracil plus leucovorin in patients with metastatic colorectal cancer, with reduced toxicity.

This was an open lable, pilot translational clinical pharmacology study of a brief (7 day) course of UFT, 300 mg/m²/day, in combination with leucovorin, 90 mg/day, in six patients with newly diagnosed advanced colorectal cancer.

In a step toward a clinical trial, the tumor response and survival of a weekday-on/weekend-off schedule of UFT was compared with its conventional daily schedule in a cancer-bearing rat model. The dose-intensive schedule-600 mg of UFT for 5 days followed by 2 drug-free days-amounts to a weekly dose similar to the conventional schedule of 400 mg/day. The weekday-on/weekend-off schedule provided increased survival and significantly greater antitumor activity than the conventional daily schedule, with no difference in adverse reactions.

Over the past decade, increasing data have emphasized both the importance of dihydropyrimidine dehydrogenase (DPD), the initial, rate-limiting enzyme in the catabolism of fluorouracil (5-FU), and its role as a control step in 5-FU metabolism, regulating the availability of 5-FU for anabolism.

This phase I study was undertaken to define the maximum tolerated dose, the dose-limiting toxicity, and the recommended dose of UFT plus leucovorin and vinorelbine in combination treatment of patients with metastatic breast cancer previously treated with one chemotherapy regimen. The pharmacokinetics of UFT and vinorelbine were also evaluated.

This article describes the design and early results of an open-label, nonrandomized phase I/II trial of oral UFT plus leucovorin therapy in combination with bolus injections of epirubicin and cyclophosphamide in patients with advanced or metastatic breast cancer. This study was designed as a cohort dose-escalation study with the principal aims being to determine dose-limiting toxicity, overall toxicity, maximum tolerated dose, tumor response, and time to disease progression.