title: Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer.
abstract: This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m(-2), intravenous bolus) followed by docetaxel (60, 75 or 85 mg m(-2), 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m(-2) with cyclophosphamide 600 mg m(-2), the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22-61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m(-2) in combination with cyclophosphamide 600 mg m(-2) every three weeks for phase II evaluation.
authors.affiliation: Department of Medical Oncology, Cancer Research UK, West of Scotland Clinical Trials Unit, Beatson Oncology Centre, E Block, Western Infirmary, Glasgow, G11 6NT, Scotland, UK. P.Vasey@beatson.gla.ac.uk
authors.forename: P A
authors.initials: PA
authors.lastname: Vasey
authors.forename: H
authors.initials: H
authors.lastname: Roché
authors.forename: D
authors.initials: D
authors.lastname: Bisset
authors.forename: C
authors.initials: C
authors.lastname: Terret
authors.forename: L
authors.initials: L
authors.lastname: Vernillet
authors.forename: A
authors.initials: A
authors.lastname: Riva
authors.forename: C
authors.initials: C
authors.lastname: Ramazeilles
authors.forename: N
authors.initials: N
authors.lastname: Azli
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D043823:Taxoids
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D003520:Cyclophosphamide; D017239:Paclitaxel