A Phase I Trial of Weekly Paclitaxel Plus Prolonged Oral Eniluracil/5‐Fluorouracil in Patients with Refractory Malignancies

• Published in: The oncologist (Dayton, Ohio) Ohio), 2002-01, Vol.7 (5), p.444-450
• Main Authors: Jones, Suzanne F., Greco, F. Anthony, Hainsworth, John D., Patton, Jeffrey W., Barton, John H., Willcutt, Noel T., Baker, Margaret N., McGuirt, Paul V., Levin, Jeremey, Burris, Howard A.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast Neoplasms - drug therapy; Clinical trials; Drug Administration Schedule; Female; Fluorouracil; Fluorouracil - administration & dosage; Humans; Infusions, Intravenous; Paclitaxel; Paclitaxel - administration & dosage; Phase I; Pyrimidine; Treatment Outcome; Uracil - administration & dosage; Uracil - analogs & derivatives
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.7-5-444

Purpose. This phase I study was conducted to determine the dose‐limiting toxicity (DLT), maximum‐tolerated doses, and recommended phase II doses of the combination of weekly intravenous paclitaxel and oral eniluracil/5‐fluorouracil (5‐FU). Patients and Methods. Patients received paclitaxel i.v. over 1 hour weekly for four consecutive weeks of each cycle. Oral eniluracil/5‐FU was administered orally twice daily for 28 consecutive days starting on day 1 of each cycle. Cycles were repeated every 35 days. Patients were accrued at six different dosing combinations. Weekly paclitaxel doses ranged from 60 mg/m2 to 80 mg/m2, and oral eniluracil/5‐FU doses ranged from 8.0/0.8 mg/m2 to 11.5/1.15 mg/m2 twice daily. Results. Thirty‐seven patients received 126 cycles of therapy. Myelosuppression was minimal at all dose levels, with no grade 4 neutropenia or thrombocytopenia reported. DLT was reported in three out of six patients enrolled at the highest dose level and consisted of grade 3 diarrhea (two patients) and grade 3 mucositis (one patient). No DLTs were reported in patients enrolled at lower dose levels. One complete response and three partial responses were reported in patients with taxane‐resistant metastatic breast cancer. Conclusion. The combination of paclitaxel and eniluracil/5‐FU was generally well tolerated. The recommended doses for further phase II testing are paclitaxel 80 mg/m2 i.v. weekly for 4 weeks plus eniluracil/ 5‐FU 10.0/1.0 mg/m2 orally twice daily on days 1‐28 with cycles repeated every 35 days.