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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

From Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX; QE2 Health Sciences Center, Nova Scotia Cancer Center, Halifax, Nova Scotia, Canada; and Duke University Medical Center, Durham; Division of Hematology/Oncology, University of North Carolina School of Medicine, Chapel Hill; and GlaxoSmithKline, Research Triangle Park, NC.

Address reprint requests to Edgardo Rivera, MD, Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Box 424, Houston, TX 77030; email: erivera{at}notes.mdacc.tmc.edu

PURPOSE: 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.

PATIENTS AND 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/m² 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.

CONCLUSION: 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.

Presented at the Fourteenth Chemotherapy Foundation Symposium, New York, NY, November 11-13, 1998; Twenty-Third Congress of the European Society for Medical Oncology, Athens, Greece, November 6-10, 1998; and Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-19, 1998.

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