Multicenter phase II study of a 28-day regimen of orally administered eniluracil and fluorouracil in the treatment of patients with anthracycline- and taxane-resistant advanced breast cancer.
OBJECTIVE
Eniluracil (776C85), a potent inactivator of dihydropyrimidine dehydrogenase, allows fluorouracil (5-FU) to be administered orally on a schedule that simulates continuous-infusion 5-FU. The primary objective of this study was to estimate the objective tumor response rate of orally administered eniluracil and 5-FU in the treatment of anthracycline- and taxane-resistant advanced breast cancer.


METHODS
Patients with anthracycline- and taxane-resistant advanced breast cancer were enrolled onto this open-label, phase II, multicenter study. Patients received orally administered 5-FU 1.0 mg/m(2) with eniluracil given in a 10:1 ratio (eniluracil:5-FU) twice daily for the first 28 days of each 35-day cycle.


RESULTS
Eighty-four patients were enrolled. Eight partial responses were observed in 84 patients (10%; 95% confidence interval [CI], 4.2% to 17.9%), and 20 patients (24%) had stable disease. The median duration of partial response was 20.1 weeks (95% CI, 12 to 26.7 weeks). The median duration of progression-free survival and overall survival for all patients was 9.9 weeks and 40.4 weeks, respectively. Most adverse events were grade 1 or 2 in intensity. Diarrhea, nausea, malaise/fatigue, vomiting, and mucositis were the most common treatment-related nonhematologic adverse events. The most frequently occurring grade 3 or 4 treatment-related adverse events were malaise/fatigue and diarrhea, occurring in 17% and 7% of patients, respectively. The incidence of grade 3 or 4 hematologic toxicity was low. Grade 3 or 4 hyperbilirubinemia occurred in 17% of patients.


CONCLUSIONS
Eniluracil-5-FU has modest antitumor activity and an acceptable safety profile in anthracycline- and taxane-resistant breast cancer. Treatment was convenient, and patient compliance was high.
Rivera
Edgardo
E
Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. erivera@notes.mdacc.tmc.edu
Sutton
Linda
L
Colwell
Bruce
B
Graham
Mark
M
Frye
Debra
D
Somerville
Matt
M
Conklin
Heather S
HS
McGuirt
Chip
C
Levin
Jeremey
J
Hortobagyi
Gabriel N
GN
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010349:Patient Compliance; D043823:Taxoids; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D043823:Taxoids; C080625:taxane; C073482:eniluracil; D014498:Uracil; D005472:Fluorouracil