title: Phase II trial of docetaxel and vinorelbine in patients with advanced non-small-cell lung cancer.
abstract: OBJECTIVE
  Docetaxel and vinorelbine are active agents in advanced non-small-cell lung cancer (NSCLC) and demonstrate preclinical synergism perhaps, in part, through their inactivation of the proto-oncogene bcl-2. We show that docetaxel (60 mg/m(2)) and vinorelbine (45 mg/m(2)) can be safely combined when given on an every 2-week schedule with filgrastim, with encouraging antitumor activity observed.
  
  
  METHODS
  Thirty-five chemotherapy naïve patients with advanced NSCLC received vinorelbine as an intravenous push immediately followed by docetaxel as a 1-hour intravenous infusion once every 2 weeks. Prophylactic corticosteroids, ciprofloxacin, and filgrastim were used.
  
  
  RESULTS
  We delivered median doses of 450 mg/m(2) of vinorelbine and 600 mg/m(2) of docetaxel. The major objective response rate was 51% (95% confidence interval [CI], 34% to 68%). With a median follow-up of 14 months, the predicted median survival time was 14 months, and the 1-year survival rate was 60% (95% CI, 44% to 80%). Febrile neutropenia occurred in five patients and five (1.3%) of 384 treatments. No dose-limiting neurotoxicity occurred. Symptomatic onycholysis and excessive lacrimation were observed after several months or more of therapy.
  
  
  CONCLUSIONS
  Docetaxel 60 mg/m(2) and vinorelbine 45 mg/m(2), both given every 2 weeks, is a highly active combination for the treatment of advanced NSCLC. Filgrastim largely obviates neutropenic fever and allows for the single-agent dose-intensity of both drugs to be delivered. The occurrence of certain late toxicities can limit use in some cases and suggests that the combination could also be beneficial in settings requiring briefer, fixed periods of treatment, such as in induction or postoperative therapy.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, and Departments of Medicine and Radiology, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY 10021, USA. millerv@mskcc.org
authors.forename: V A
authors.initials: VA
authors.lastname: Miller
authors.forename: L M
authors.initials: LM
authors.lastname: Krug
authors.forename: K K
authors.initials: KK
authors.lastname: Ng
authors.forename: B
authors.initials: B
authors.lastname: Pizzo
authors.forename: W
authors.initials: W
authors.lastname: Perez
authors.forename: R T
authors.initials: RT
authors.lastname: Heelan
authors.forename: M G
authors.initials: MG
authors.lastname: Kris
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D016019:Survival Analysis; D043823:Taxoids; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D014747:Vinblastine; D017239:Paclitaxel; D000069585:Filgrastim; D000077235:Vinorelbine