title: Vinorelbine/docetaxel combination treatment of metastatic breast cancer: a phase I study.
abstract: OBJECTIVE
  The aim of this study was to investigate the combination of vinorelbine (VRL) alternating intravenous (i.v.) and oral in combination with docetaxel (DCT) as first-line chemotherapy of patients with metastatic breast cancer.
  
  
  METHODS
  Tested doses were 60 or 70 mg m(-2) given on day 1 for DCT, 20 to 25 mg m(-2) for i.v. VRL on day 1, 60 mg m(-2) on day 8 or day 15 for oral VRL. Day 1 was administered every 3 weeks. Three to six patients were treated per dose level.
  
  
  RESULTS
  The median age of the 30 treated patients was 60 years. Four patients were non evaluable for the maximum tolerated dose (MTD) and were replaced. Reported dose-limiting toxicities were 11 omissions of oral VRL for neutropenia, two cases of febrile neutropenia and two grade 4 neutropenia >or=7 days. Dose levels using DCT doses >60 mg m(-2) and/or i.v. VRL doses >20 mg m(-2) met the criteria for MTD. Most frequent toxicities were febrile neutropenia in seven patients and neutropenic infection in four patients (one fatal). Therefore, the recommended schedule was established at i.v. VRL 20 mg m(-2) with DCT 60 mg m(-2) on day 1 and oral VRL 60 mg m(-2) given on day 15 every 3 weeks. At this recommended schedule, only one of six patients experienced febrile neutropenia. Among 22 patients evaluable for tumour response, 2 complete and 10 partial responses were reported. Pharmacokinetics of combined VRL and DCT demonstrated the absence of mutual interaction.
  
  
  CONCLUSIONS
  This phase I study established the recommended doses and schedules of the combination alternating i.v. and oral VRL with DCT, this recommended regimen being further explored in a phase II study.
authors.affiliation: Centre Oscar Lambret, 3, rue Frédéric Combemale, B.P. 307, Lille Cedex 59020, France. j-bonneterre@o-lambret.fr
authors.forename: J
authors.initials: J
authors.lastname: Bonneterre
authors.forename: M
authors.initials: M
authors.lastname: Campone
authors.forename: P
authors.initials: P
authors.lastname: Koralewski
authors.forename: M
authors.initials: M
authors.lastname: Blasinska-Morawiec
authors.forename: R
authors.initials: R
authors.lastname: Deporte-Fety
authors.forename: E
authors.initials: E
authors.lastname: Chatelut
authors.forename: F
authors.initials: F
authors.lastname: Leger
authors.forename: B
authors.initials: B
authors.lastname: Longerey
authors.forename: L
authors.initials: L
authors.lastname: Ecochard
authors.forename: I
authors.initials: I
authors.lastname: Douville
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D018450:Disease Progression; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005602:France; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011044:Poland; D043823:Taxoids / Q000008:administration & dosage / Q000633:toxicity; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D000077235:Vinorelbine
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D000077235:Vinorelbine