UFT/leucovorin plus vinorelbine combination for advanced breast cancer

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. Patients were treated with escalating doses of UFT and vinorelbine, given every 4 weeks. At least three patients were treated at each dose level before escalating to the next level. As of September 1, 1999, 22 patients have been treated. Eighteen patients were evaluable for antitumor response. One patient had a complete response (which was obtained after three cycles); four patients had a partial response. The area under the concentration-time curve (AUC0-6 h) of 5-fluorouracil increase was more than dose-proportional. The AUC0-6 h values of fluorouracil were significantly higher than those noted for the four patients who developed dose-limiting toxicity at day 15. The removal of one administration of vinorelbine at dose levels 3 and 4 has allowed for increased UFT dosage and AUC0-6 h of fluorouracil, with no dose-limiting toxicity reported for these patients. No pharmacokinetic interaction between UFT and vinorelbine was observed.