Fax (713) 794-4385
Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma
Article first published online: 25 APR 2002
Copyright © 2002 American Cancer Society
Volume 94, Issue 9, pages 2321–2326, 1 May 2002
How to Cite
Rivera, E., Valero, V., Cristofanilli, M., Frye, D. K., Booser, D. J., Rosales, M. M. and Hortobagyi, G. N. (2002), Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma. Cancer, 94: 2321–2326. doi: 10.1002/cncr.10488
- Issue published online: 25 APR 2002
- Article first published online: 25 APR 2002
- Manuscript Accepted: 4 OCT 2001
- Manuscript Received: 15 AUG 2001
- Glaxo Wellcome Inc. (Research Triangle Park, NC)
- metastatic breast carcinoma;
- antitumor activity;
- dose-limiting toxicities
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.
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.
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. Cancer 2002;94:2321–6. © 2002 American Cancer Society.