title: Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract.
abstract: OBJECTIVE
  Vinflunine (VFL) is a new microtubule inhibitor that has activity against transitional cell carcinoma of urothelial tract (TCCU). We conducted a randomized phase III study of VFL and best supportive care (BSC) versus BSC alone in the treatment of patients with advanced TCCU who had experienced progression after a first-line platinum-containing regimen.
  
  
  METHODS
  The study was designed to compare overall survival (OS) between patients receiving VFL + BSC (performance status [PS] = 0: 320 mg/m(2), every 3 weeks; PS = 0 with previous pelvic radiation and PS = 1: 280 mg/m(2) subsequently escalated to 320 mg/m(2)) or BSC.
  
  
  RESULTS
  Three hundred seventy patients were randomly assigned (VFL + BSC, n =253; BSC, n = 117). Both arms were well balanced except there were more patients with PS more than 1 (10% difference) in the BSC arm. Main grade 3 or 4 toxicities for VFL + BSC were neutropenia (50%), febrile neutropenia (6%), anemia (19%), fatigue (19%), and constipation (16%). In the intent-to-treat population, the objective of a median 2-month survival advantage (6.9 months for VFL + BSC v 4.6 months for BSC) was achieved (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12) but was not statistically significant (P = .287). Multivariate Cox analysis adjusting for prognostic factors showed statistically significant effect of VFL on OS (P = .036), reducing the death risk by 23% (HR = 0.77; 95% CI, 0.61 to 0.98). In the eligible population (n = 357), the median OS was significantly longer for VFL + BSC than BSC (6.9 v 4.3 months, respectively), with the difference being statistically significant (P = .040). Overall response rate, disease control, and progression-free survival were all statistically significant favoring VFL + BSC (P = .006, P = .002, and P = .001, respectively).
  
  
  CONCLUSIONS
  VFL demonstrates a survival advantage in second-line treatment for advanced TCCU. Consistency of results exists with significant and meaningful benefit over all efficacy parameters. Safety profile is acceptable, and therefore, VFL seems to be a reasonable option for TCCU progressing after first-line platinum-based therapy.
authors.affiliation: Department of Medical Oncology, University Hospital Del Mar, Passeig Marítim 25-29, E-08003 Barcelona, Spain. jbellmunt@imas.imim.es
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Christine
authors.initials: C
authors.lastname: Théodore
authors.forename: Tomasz
authors.initials: T
authors.lastname: Demkov
authors.forename: Boris
authors.initials: B
authors.lastname: Komyakov
authors.forename: Lisa
authors.initials: L
authors.lastname: Sengelov
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.forename: Armelle
authors.initials: A
authors.lastname: Caty
authors.forename: Joan
authors.initials: J
authors.lastname: Carles
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jagiello-Gruszfeld
authors.forename: Oleg
authors.initials: O
authors.lastname: Karyakin
authors.forename: François-Michel
authors.initials: FM
authors.lastname: Delgado
authors.forename: Patrick
authors.initials: P
authors.lastname: Hurteloup
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Nassim
authors.initials: N
authors.lastname: Morsli
authors.forename: Yacine
authors.initials: Y
authors.lastname: Salhi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Culine
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D006801:Humans; D008875:Middle Aged; D010166:Palliative Care; D017671:Platinum Compounds / Q000008:administration & dosage; D016019:Survival Analysis; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000556:secondary; D019459:Urothelium / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D017671:Platinum Compounds; C111217:vinflunine; D014747:Vinblastine