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A phase 2 study of a fixed combination of uracil and ftorafur and leucovorin given orally in a twice‐daily regimen to treat patients with recurrent metastatic breast cancer
Author(s) -
Hortobagyi Gabriel N.,
Young Robyn R.,
Karwal Mark,
Ibrahim Nuhad K.,
Hermann Robert,
Murray James L.,
Watkins Stanley P.,
Gore Ira
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.25042
Subject(s) - medicine , regimen , gastroenterology , nausea , population , adverse effect , phases of clinical research , metastatic breast cancer , fluorouracil , dosing , cancer , progressive disease , clinical endpoint , breast cancer , toxicity , chemotherapy , surgery , clinical trial , environmental health
BACKGROUND: UFT, a combination of uracil and ftorafur, was developed to combine the cytotoxic effects of 5‐fluorouracil (5‐FU) with convenient oral dosing. Leucovorin is combined with UFT to further potentiate the effect of 5‐FU on tumor cells. Orally administered UFT and leucovorin provide higher peak plasma concentrations of 5‐FU and prolonged therapeutic 5‐FU concentrations compared with continuous infusion of 5‐FU. METHODS: Ninety‐four 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 , which was given in 2 divided doses every 12 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (OR = complete response [CR] + partial response [PR]) and overall survival (OS). RESULTS: Of the 94 patients enrolled, 68 were evaluable for efficacy. Although no CRs were observed, 9 patients achieved PRs, for an OR of 13.2% in the evaluable population. The median TTP for the evaluable population was 10.3 weeks, and the proportion of patients free of disease progression at 6 months was 17%. The median OS was 61.6 weeks for all patients enrolled. The most common drug‐related ≥ grade 3 adverse events (graded using the National Cancer Institute Common Toxicity Criteria version 2) were diarrhea, asthenia, nausea, and dehydration. CONCLUSIONS: The combination of UFT and leucovorin administered orally in a twice‐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.