title: Randomized trial of vinorelbine compared with fluorouracil plus leucovorin in patients with stage IV non-small-cell lung cancer.
abstract: OBJECTIVE
  This prospective randomized trial was performed to compare the effectiveness of intravenous vinorelbine tartrate with intravenous fluorouracil and leucovorin (5-FU/LV) on the primary end points of survival, quality of life (QOL), and relief of cancer-related symptoms in patients with advanced non-small-cell lung cancer (NSCLC). Secondary end points included tumor response rates and time to treatment failure. In addition, the safety of both treatment regimens was evaluated in this multicenter study.
  
  
  METHODS
  Two hundred sixteen patients with stage IV NSCLC were enrolled onto this study from 18 centers. Vinorelbine was administered at a dose of 30 mg/m2/wk. 5-FU/LV was administered at a dose of 425 mg/m2 and 20 mg/m2, respectively, for 5 consecutive days every 4 weeks. Patients with progressive disease or toxicity were removed from study while responding and stable patients were continued on therapy.
  
  
  RESULTS
  The median survival time of patients who received vinorelbine was 30 weeks, with 25% of patients alive at 1 year, compared with a median survival time of 22 weeks and 16% of patients alive at 1 year for those treated with 5-FU/LV (P = .03, log-rank test). This improvement in survival was associated with a higher objective response rate (12% v 3%) and time to treatment failure (10 weeks v 8 weeks) for vinorelbine versus 5-FU/LV. The dose-limiting toxicity of vinorelbine was granulocytopenia, with 54% of patients experiencing grade 3/4 granulocytopenia. Nonhematologic toxicity of vinorelbine was generally grade 1 or 2. The most common grade 3 toxicities were related to injection-site reactions.
  
  
  CONCLUSIONS
  This trial confirms the efficacy of vinorelbine in patients with advanced NSCLC. The clinical activity and relatively favorable toxicity profile of this agent make it a reasonable and useful treatment option in the management of patients with this disease.
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA. crawf006@mc.duke.edu
authors.forename: J
authors.initials: J
authors.lastname: Crawford
authors.forename: M
authors.initials: M
authors.lastname: O'Rourke
authors.forename: J H
authors.initials: JH
authors.lastname: Schiller
authors.forename: C H
authors.initials: CH
authors.lastname: Spiridonidis
authors.forename: S
authors.initials: S
authors.lastname: Yanovich
authors.forename: H
authors.initials: H
authors.lastname: Ozer
authors.forename: A
authors.initials: A
authors.lastname: Langleben
authors.forename: L
authors.initials: L
authors.lastname: Hutchins
authors.forename: A
authors.initials: A
authors.lastname: Koletsky
authors.forename: G
authors.initials: G
authors.lastname: Clamon
authors.forename: S
authors.initials: S
authors.lastname: Burman
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Hohneker
authors.forename: C H
authors.initials: CH
authors.lastname: Spiridonitis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced; D000931:Antidotes / Q000008:administration & dosage; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011788:Quality of Life; D016019:Survival Analysis; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine; D002955:Leucovorin; D000077235:Vinorelbine; D005472:Fluorouracil