title: Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel-cisplatin versus vinorelbine-cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study.
abstract: BACKGROUND
  This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Overall, 115 patients received DC (docetaxel 75 mg/m(2) and cisplatin 100 mg/m(2) both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m(2)/week on days 1 and 8 and cisplatin 100 mg/m(2) on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m(2) days 1 and 8 (A2), or docetaxel 100 mg/m(2), day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR).
  
  
  RESULTS
  Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms A1 and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC.
  
  
  CONCLUSIONS
  The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of long-term survivors, despite the absence of efficacy of the second-line in our study.
authors.affiliation: Centre René Gauducheau, Saint Herblain, France. jy-douillard@nantes.fnclcc.fr
authors.forename: J-Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: R
authors.initials: R
authors.lastname: Gervais
authors.forename: G
authors.initials: G
authors.lastname: Dabouis
authors.forename: A
authors.initials: A
authors.lastname: Le Groumellec
authors.forename: M
authors.initials: M
authors.lastname: D'Arlhac
authors.forename: D
authors.initials: D
authors.lastname: Spaeth
authors.forename: B
authors.initials: B
authors.lastname: Coudert
authors.forename: D
authors.initials: D
authors.lastname: Caillaud
authors.forename: A
authors.initials: A
authors.lastname: Monnier
authors.forename: C
authors.initials: C
authors.lastname: Clary
authors.forename: B
authors.initials: B
authors.lastname: Maury
authors.forename: M
authors.initials: M
authors.lastname: Mornet
authors.forename: A
authors.initials: A
authors.lastname: Rivière
authors.forename: P
authors.initials: P
authors.lastname: Clouet
authors.forename: C
authors.initials: C
authors.lastname: Couteau
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018592:Cross-Over Studies; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine