Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma

PURPOSE. The authors conducted a single-institution Phase I clinical trial to determine the maximum tolerated doses and to define the toxic effects of oral eniluracil and oral 5-fluorouracil (5-FU) combined with docetaxel in patients with metastatic breast carcinoma. PATIENTS AND METHODS. Patients with metastatic breast carcinoma were eligible if they had disease progression after anthracycline-based therapy and had never been exposed to taxanes. The starting doses of oral eniluracil and oral 5-FU were 11.5 mg/m² and 1.15 mg/m², respectively, twice daily on Days 1-14. Docetaxel was given intravenously at a starting dose of 50 mg/m² on Day 1 only. The dose of docetaxel was escalated among cohorts until a maximum tolerated dose was reached. Courses were repeated every 21 days. RESULTS. The authors treated 19 patients with Stage IV breast carcinoma, of whom 5 had received prior chemotherapy for their metastatic disease. Fifty-three percent had a performance status of 1, and 53% had bone or soft tissue involvement as the dominant site of disease. All patients had received prior therapy with doxorubicin. The dose-limiting toxicity was neutropenic fever. No episodes of sepsis were observed. Significant antitumor activity was observed with a total of two complete and nine partial responses. The recommended doses for Phase II studies are 72 mg/m² docetaxel on Day 1 and 10.0/1.0 mg/m² oral eniluracil/5-FU twice daily for a total of 14 days, with courses being repeated every 21 days. CONCLUSIONS. The combination of oral eniluracil/5-FU and intravenous docetaxel is a safe and well tolerated regimen. Significant antitumor activity is associated with this combination.