title: Phase I/II and pharmacokinetic study of intravenous vinflunine in combination with cisplatin for the treatment of chemonaive patients with advanced non-small-cell lung cancer.
abstract: BACKGROUND
  A multicenter phase I/II trial of vinflunine administered in combination with cisplatin at 80 mg/m(2) was conducted in order to determine the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose of the combination. An eventual mutual pharmacokinetic drug-drug interaction when vinflunine and cisplatin were coadministered was also evaluated. The study was also intended to define the response rate of vinflunine in combination with cisplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) at the recommended dose.
  
  
  METHODS
  Patients were required to have a histologically confirmed diagnosis of NSCLC not amenable to curable treatment or stage IV disease. Patients may have had previous surgery for NSCLC but were to be chemonaive and have at least 1 bidimensional measurable lesion outside an irradiated area.
  
  
  RESULTS
  The recommended dose was established at cisplatin 80 mg/m2 combined with vinflunine 320 mg/m(2). No unexpected adverse events were seen. Pharmacokinetic analysis supported the absence of mutual pharmacokinetic interaction when vinflunine and cisplatin are given in combination. Treatment of 53 patients at this recommended dose demonstrated a tumor response rate of 32.1% in the intent-to-treat population; disease control was achieved in 79.2% of the patients. The median progression-free survival and overall survival were estimated at 5 months and 10.4 months, respectively, and the 1-year survival rate was 43.4%.
  
  
  CONCLUSIONS
  These results place the vinflunine/cisplatin combination among the most active doublets in this treatment setting and warrant further development in phase III trials of first-line treatment of patients with advanced metastatic NSCLC.
authors.affiliation: CH Lyon Sud, Pierre Bénite, France.
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Rodrig
authors.initials: R
authors.lastname: Ramlau
authors.forename: Xu-Shan
authors.initials: XS
authors.lastname: Sun
authors.forename: Guillermo
authors.initials: G
authors.lastname: Lopez-Vivanco
authors.forename: Christian
authors.initials: C
authors.lastname: Puozzo
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Pouget
authors.forename: Marie Claire
authors.initials: MC
authors.lastname: Pinel
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: C111217:vinflunine; D014747:Vinblastine; D002945:Cisplatin