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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
Author(s) -
Hortobagyi Gabriel N.,
Heim William,
Hutchins Laura,
Rivera Edgardo,
Mason Bernard,
Booser Daniel J.,
Kirshner Jeffrey
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24900
Subject(s) - medicine , nausea , gastroenterology , regimen , vomiting , population , phases of clinical research , adverse effect , metastatic breast cancer , clinical endpoint , progressive disease , cancer , chemotherapy , surgery , breast cancer , clinical trial , environmental health
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 ≥ 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. Cancer 2010. © 2010 American Cancer Society.