title: Phase I study of eniluracil and oral 5-fluorouracil in combination with docetaxel in the treatment of patients with metastatic breast carcinoma.
abstract: OBJECTIVE
  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.
  
  
  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/m(2) and 1.15 mg/m(2), respectively, twice daily on Days 1-14. 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. 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/m(2) docetaxel on Day 1 and 10.0/1.0 mg/m(2) 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.
authors.affiliation: Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030-4009, USA. eriviera@notes.mdacc.tmc.edu
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Debra K
authors.initials: DK
authors.lastname: Frye
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Booser
authors.forename: Marguerite M
authors.initials: MM
authors.lastname: Rosales
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D000077143:Docetaxel; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D043823:Taxoids; D014498:Uracil / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D043823:Taxoids; D000077143:Docetaxel; C073482:eniluracil; D014498:Uracil; D017239:Paclitaxel; D005472:Fluorouracil