A phase 2 study of a fixed combination of uracil and ftorafur (UFT) and leucovorin given orally in a 3-times-daily regimen to treat patients with recurrent metastatic breast cancer

Background: A combination of uracil and ftorafur (UFT) was developed to combine the cytotoxic effects of 5-fluorouracil (5-FU) with convenient oral dosing. Leucovorin was combined with UFT to further potentiate the effect of 5-FU on tumor cells. Orally administered UFT and leucovorin provided higher peak plasma concentrations of 5-FU and prolonged therapeutic 5-FU concentrations compared with continuous infusion of 5-FU.

Methods: Ninety-one patients with metastatic breast Cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35-day cycle. The total daily dose of UFT was 300 mg/m(2), administered in 3 doses of 100 mg/m(2) each every 8 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (overall response equals complete response plus partial response) and overall survival.

Results: Of the 91 patients enrolled, 70 were evaluable for efficacy. Although no complete responses were observed, 7 patients had partial responses, for an overall response rate of 10% in the evaluable population. The median TTP for the evaluable population was 10 weeks, and the proportion of patients who were free of disease progression at 6 months was 23%. The median overall survival was 59.4 weeks for all patients enrolled. Common, drug-related > or = grade 3 adverse events (graded according to National Cancer Institute Common Toxicity Criteria, version 2) included diarrhea, vomiting, abdominal pain, and nausea.

Conclusions: The combination of UFT and leucovorin administered orally in a 3-times-daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast Cancer previously treated with anthracyclines and/or taxanes.