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.
Hortobagyi
Gabriel N
GN
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 424, Houston, TX 77030-4009, USA. ghortoba@mdanderson.org
Heim
William
W
Hutchins
Laura
L
Rivera
Edgardo
E
Mason
Bernard
B
Booser
Daniel J
DJ
Kirshner
Jeffrey
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012008:Recurrence; D019233:Retreatment; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D005641:Tegafur; D014498:Uracil; D002955:Leucovorin