Low-dose oral fluorouracil with eniluracil as first-line chemotherapy against advanced breast cancer: A phase II study

Purpose: Eniluracil (776C85) is an effective inactivator of dihydropyrimidi ne dehydrogenase that allows continuous low-dose oral fluorouracil (5-FU) t o be given with predicable oral bioavailability. We have assessed this as f irst-line oral chemotherapy for patients with advanced/metastatic breast ca ncer. Patients and Methods: Patients with histologically proven, locally advanced or metastatic breast cancer without previous chemotherapy for advanced dis ease were entered onto this open-label phase II study Patients received ora l 5-FU 1.0 mg/m(2) with eniluracil 10 mg/m(2), both given twice daily for t he first 28 days of each 35-day cycle, continuing until disease progression or unmanageable toxicity. Results: Thirty-three patients were entered, with a median age of 53 years. Sixteen partial responses were seen in twenty-nine assessable patients (55 %; 95% confidence interval, 37% to 73%), including responses in four (40%) out of 10 patients who had received prior adjuvant 5-FU. Seven patients had stable disease for at least 3 months with symptom improvement. Median resp onse duration wets 14 months (range, 10 to 18+ months). Toxicity was low. T here were only two episodes of drug-related grade 3 nonhematologic toxicity (diarrhea and infection), and only 6%, 3%, and 3% of patients developed gr anulocytopenia, thrombocytopenia, and neutropenic sepsis, respectively. Mil d (grade 1/2) diarrhea occurred in 39% of patients, hand-fool syndrome in 1 5%, nausea in 27%, and mucositis in 18%. Toxicity-associated delay and dose reduction occurred in only 2% and 5% of courses, respectively. Conclusion: first-line treatment with the combination of oral 5-FU and enil uracil has high activity in patients with advanced breast cancer comparable with the most active conventional cytotoxic agents but with strikingly les s toxicity. J Clin Oncol 18:2378-2384, (C) 2000 by American Society of Clin ical Oncology.