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.

Abstract

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.

• Authors: Gabriel N Hortobagyi, William Heim, Laura Hutchins, Edgardo Rivera, Bernard Mason, Daniel J Booser, Jeffrey Kirshner
• Journal: Cancer (Cancer) Vol. 116 Issue 6 Pg. 1440-5 (Mar 15 2010) ISSN: 0008-543X [Print] United States
• PMID: 20091835 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tegafur
• Uracil
• Leucovorin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Drug Administration Schedule
• Female
• Humans
• Leucovorin (administration & dosage)
• Middle Aged
• Neoplasm Metastasis
• Recurrence
• Retreatment
• Tegafur (administration & dosage)
• Uracil (administration & dosage)