A phase I trial of weekly paclitaxel plus prolonged oral eniluracil/5-fluorouracil in patients with refractory malignancies.
OBJECTIVE
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).


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/m(2) to 80 mg/m(2), and oral eniluracil/5-FU doses ranged from 8.0/0.8 mg/m(2) to 11.5/1.15 mg/m(2) 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.


CONCLUSIONS
The combination of paclitaxel and eniluracil/5-FU was generally well tolerated. The recommended doses for further phase II testing are paclitaxel 80 mg/m(2) i.v. weekly for 4 weeks plus eniluracil/ 5-FU 10.0/1.0 mg/m(2) orally twice daily on days 1-28 with cycles repeated every 35 days.
Jones
Suzanne F
SF
The Sarah Cannon Cancer Center and Tennessee Oncology, Nashville 37203, USA.
Greco
F Anthony
FA
Hainsworth
John D
JD
Patton
Jeffrey W
JW
Barton
John H
JH
Willcutt
Noel T
NT
Baker
Margaret N
MN
McGuirt
Paul V
PV
Levin
Jeremey
J
Burris
Howard A
HA
D000284:Administration, Oral; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000964:Antimetabolites, Antineoplastic; C073482:eniluracil; D014498:Uracil; D017239:Paclitaxel; D005472:Fluorouracil