Phase I trial of uracil-ftorafur, leucovorin, and etoposide: an active all-oral regimen for metastatic breast cancer.
OBJECTIVE
To determine the maximum tolerated doses, toxicities, and therapeutic effect of an oral chemotherapy regimen consisting of uracil-ftorafur, etoposide, and leucovorin for metastatic breast cancer.


METHODS
The regimen consists of 28-day cycles of uracil-ftorafur, etoposide, and leucovorin administered orally on days 1-14. The dose of etoposide was fixed at 50 mg/m2/day, and uracil-ftorafur was escalated in 50 mg/m2/day increments from 200 to 350 mg/m2. Leucovorin, was used at a dose of 90 mg/day. Eligibility criteria required prior treatment with a taxane or anthracycline.


RESULTS
A total of 23 patients were enrolled. Twenty patients are assessable for toxicity and 16 patients are assessable for response. All non-hematologic toxicities were grade 1 or 2. Three hematologic dose-limiting toxicities (DLTs) were observed. Partial responses were seen in 6 of 16 (37.5%, 95% confidence interval 15%, 85%) of assessable patients with durations ranging from 4 to 20 months. Stable disease was observed in 4 of 16 (25%) of patients with durations from 4 to 12 months. Median time to progression was 10.5 months. An intent to treat analysis revealed a response of 26%.


CONCLUSIONS
The recommended dose and schedule of this combination is uracil-ftorafur 350 mg/m2, leucovorin 90 mg/day, and etoposide 50 mg/m2 for two consecutive weeks in a 4-week cycle. This all-oral regimen is well tolerated and demonstrates encouraging efficacy in a cohort of heavily pretreated patient with metastatic breast cancer.
Hartman
Anne-Renee
AR
Division of Oncology, Stanford University School of Medicine, Stanford, CA 94305-5151, USA.
Grekowicz
Amy
A
Lum
Bert L
BL
Carlson
Robert W
RW
Schurman
Christine
C
Sikic
Branimir I
BI
Shapiro
Richard
R
Stockdale
Frank E
FE
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
D005641:Tegafur; D014498:Uracil; D005047:Etoposide; D002955:Leucovorin