title: Cisplatin plus weekly vinorelbine versus cisplatin plus vinorelbine on days 1 and 8 in advanced non-small cell lung cancer: a prospective randomized phase III trial of the G.O.I.M. (Gruppo Oncologico Italia Meridionale).
abstract: OBJECTIVE
  A phase III randomized trial was carried out to compare two schedules of the vinorelbine (VNR)-cisplatin (CDDP) regimen in patients with locally advanced unresectable poor prognosis stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoints were overall survival (OS) and analysis of toxicity, while secondary endpoints included response rates, time-to-progression (TTP) and quality of life (QoL).
  
  
  METHODS
  Eligible patients were randomized to receive: (a) VNR 25mg/m(2) on day 1, 8 and 15 plus CDDP 100mg/m(2) on day 1 every 4 weeks or (b) VNR 30 mg/m(2) on day 1 and 8 plus CDDP 80 mg/m(2) on day 1 every 3 weeks. All patients were chemotherapy-naïve and had an ECOG performance status (PS) of 0-1.
  
  
  RESULTS
  Overall 278 patients were enrolled into the trial. Overall response rate was 34% (95% CL 26-42%) in the weekly VNR/CDDP arm, and 32% (95% CL 24-40%) in patients treated with day 1-8 VNR/CDDP without any statistically significant difference. Median TTP was 4.5 and 4.6 months respectively for weekly VNR/CDDP arm and the day 1-8 VNR/CDDP one. This difference was not statistically significant (log-rank test, p=0.818). Median OS was 9.45 and 10 months respectively for weekly VNR/CDDP arm and the day 1-8 VNR/CDDP one without statistically a significant difference (log-rank test, p=0.259). The 1- and 2-year survival rates were 31 and 36%, and 10 and 11% respectively. The incidence of severe neutropenia (34% versus 68%; p=0.0001) and of febrile neutropenia (5% versus 12%; p=0.026), as well as the rate of therapy omissions (10% versus 24%; p=0.0037) were higher in the weekly VNR/CDDP arm than in the day 1-8 VNR/CDDP one. The weekly VNR/CDDP regimen was associated with a lower received dose intensity in a statistically significant fashion (9% versus 22%; p=0.0001) and with a lower non-statistically significant quality of life score as compared to the day 1-8 VNR/CDDP schedule.
  
  
  CONCLUSIONS
  The combination of day 1-8 VNR plus CDDP every 3 weeks is less toxic and better tolerated than the regimen of weekly VNR plus CDDP every 4 weeks. The two schedules are equivalent in terms of overall response rate, median time-to-progression and overall survival. The combination of VNR on day 1-8 plus CDDP every 3 weeks may be considered as a reference regimen for the treatment of patients with advanced disease and those who deserve a postoperative therapy, and for future studies.
authors.affiliation: Department of Experimental Oncology and Clinical Applications, University of Palermo, Italy. vittorio.gebbia@tin.it
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gebbia
authors.forename: Domenico
authors.initials: D
authors.lastname: Galetta
authors.forename: Vito
authors.initials: V
authors.lastname: Lorusso
authors.forename: Michele
authors.initials: M
authors.lastname: Caruso
authors.forename: Francesco
authors.initials: F
authors.lastname: Verderame
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pezzella
authors.forename: Nicolò
authors.initials: N
authors.lastname: Borsellino
authors.forename: Ernesto
authors.initials: E
authors.lastname: Durini
authors.forename: Roberto
authors.initials: R
authors.lastname: Valenza
authors.forename: Biagio
authors.initials: B
authors.lastname: Agostara
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D006801:Humans; D007558:Italy; D016015:Logistic Models; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D011788:Quality of Life; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine