title: Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study.
abstract: This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.
authors.affiliation: Centre Paul Papin, 2 rue Moll, F-49033, Angers, France. a.lortholary@unimedia.fr
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.forename: P
authors.initials: P
authors.lastname: Maillard
authors.forename: R
authors.initials: R
authors.lastname: Delva
authors.forename: M
authors.initials: M
authors.lastname: Boisdron-Celle
authors.forename: D
authors.initials: D
authors.lastname: Perard
authors.forename: L
authors.initials: L
authors.lastname: Vernillet
authors.forename: M
authors.initials: M
authors.lastname: Besenval
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D005472:Fluorouracil