Abstract
PURPOSE
The authors conducted a singleโinstitution Phase I clinical trial to determine the maximum tolerated doses and to define the toxic effects of oral eniluracil and oral 5โfluorouracil (5โFU) 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 anthracyclineโbased therapy and had never been exposed to taxanes. The starting doses of oral eniluracil and oral 5โFU were 11.5 mg/m^2^ and 1.15 mg/m^2^, respectively, twice daily on Days 1โ14. Docetaxel was given intravenously at a starting dose of 50 mg/m^2^ 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. Fiftyโthree 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 doseโlimiting 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/m^2^ docetaxel on Day 1 and 10.0/1.0 mg/m^2^ oral eniluracil/5โFU twice daily for a total of 14 days, with courses being repeated every 21 days.
CONCLUSIONS
The combination of oral eniluracil/5โFU and intravenous docetaxel is a safe and well tolerated regimen. Significant antitumor activity is associated with this combination. Cancer 2002;94:2321โ6. ยฉ 2002 American Cancer Society.
DOI 10.1002/cncr.10488