title: Phase I trial of docetaxel and vinorelbine in patients with advanced nonsmall cell lung carcinoma.
abstract: BACKGROUND
  With preclinical evidence of synergy, this dose-finding trial examining the combination of docetaxel and vinorelbine given with prophylactic filgrastim for the treatment of patients with nonsmall cell lung carcinoma was undertaken.
  
  
  METHODS
  Twenty-seven patients with advanced nonsmall cell lung carcinoma received vinorelbine as an intravenous push immediately followed by docetaxel as a 1-hour intravenous infusion once every 2 weeks at 1 of 7 different dose levels. Vinorelbine was escalated from 15 mg/m(2) (Level I) to 45 mg/m(2) (Level VII) and docetaxel was increased from 50 mg/m(2) (Level I) to 60 mg/m(2) (Level VII). Prophylactic corticosteroids and filgrastim were employed prospectively.
  
  
  RESULTS
  After completion of dose Level VII, accrual was terminated because Phase II dose intensity of both agents had been reached and further escalation was believed to be unsafe. At dose Level VII, one episode of first-cycle febrile neutropenia and a death after three treatment cycles due to Haemophilus influenzae sepsis (Grade 5 toxicity according to the Common Toxicity Criteria of the National Cancer Institute) without neutropenia were noted. In all, 209 treatment cycles were administered and febrile neutropenia was observed in only 4 of these treatments (1.9%). Bacteremia occurred in three patients (four episodes) in the absence of neutropenia. Symptomatic onycholysis was observed in three patients. Clinically significant peripheral neuropathy and fluid retention were rare. Confirmed partial responses were noted in 10 patients for a response rate of 37% (95% confidence interval, 20-57%).
  
  
  CONCLUSIONS
  Docetaxel at a dose of 60 mg/m(2) and vinorelbine at a dose of 45 mg/m(2), both given every 2 weeks, can be combined safely to achieve Phase II dose intensity of both agents. An ongoing Phase II trial will define the activity of this treatment combination.
authors.affiliation: Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: V A
authors.initials: VA
authors.lastname: Miller
authors.forename: K K
authors.initials: KK
authors.lastname: Ng
authors.forename: L M
authors.initials: LM
authors.lastname: Krug
authors.forename: W
authors.initials: W
authors.lastname: Perez
authors.forename: B
authors.initials: B
authors.lastname: Pizzo
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; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D011994:Recombinant Proteins; D043823:Taxoids; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D014747:Vinblastine; D017239:Paclitaxel; D000069585:Filgrastim; D000077235:Vinorelbine