A Phase I Study of UFT-Oral Vinorelbine in Metastatic Breast Cancer

Abstract

Background: Despite current treatment options, metastatic breast cancer (MBC) remains essentially incurable, requiring research on new drugs or combinations to improve survival and quality of life. Patients and Methods: This phase I study was designed to define the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose of all-oral tegafur-uracil (UFT)/folinic acid combined with vinorelbine as chemotherapy for MBC. Starting doses were 40 mg/m²/week of oral vinorelbine administered continuously and 250 mg/m²/day of UFT plus 90 mg/day of folinic acid from day 1 to day 28, followed by a 1-week rest period. Results: Ten patients were included. Eight were evaluable for toxicity and antitumor response. The second dose level was shown to be the MTD. At this dose, 2 out of 5 patients receiving oral vinorelbine at 40 mg/m²/week and UFT at 300 mg/m²/day developed DLT consisting of grade 3 asthenia and grade 3nausea despite standard prophylaxis. Other toxicities were grade 1 diarrhea and anemia. There were no treatment-related deaths. Conclusions: The recommended dose for this combination seems to be the first dose level. A stable response was observed for 6 patients (average 33 weeks). This combination appears to be well-tolerated and offers an alternative to intravenous chemotherapy.