title: Vinflunine-gemcitabine versus vinflunine-carboplatin as first-line chemotherapy in cisplatin-unfit patients with advanced urothelial carcinoma: results of an international randomized phase II trial (JASINT1).
abstract: BACKGROUND
  There is no standard first-line chemotherapy for advanced urothelial carcinoma (aUC) in cisplatin-ineligible (cisplatin-unfit) patients. The study assessed the efficacy and tolerability profile of two vinflunine-based cytotoxic regimens in this setting.
  
  
  METHODS
  Patients with aUC a creatinine clearance (CrCl) of <60 but ≥30 ml/min, performance status 0 or 1 and no prior chemotherapy for advanced disease were randomized (1 : 1). They received vinflunine 250 or 280 mg/m(2) (based on baseline CrCl) on day 1, plus either gemcitabine [750 mg/m(2) escalated to 1000 mg/m(2) in cycle 2 if no toxicity grade (G) ≥2 on days 1 and 8 (VG) or plus carboplatin area under the curve 4.5 day 1 (VC) every 21 days]. To detect a 22% improvement in each arm compared with H0 (41%) in the primary end point, disease control rate (DCR = complete response + partial response + stable disease), 31 assessable patients per arm were required (α = 5%, β = 20%).
  
  
  RESULTS
  Sixty-nine patients were enrolled (34 VG, 35 VC). Less G3/4 haematological adverse events (AEs) were reported with VG: neutropaenia was seen in 38% (versus 68% with VC) and febrile neutropaenia in 3% (versus 14% with VC) of patients. No major differences were observed for non-haematological AEs. DCR was 77% in both groups; overall response rate (ORR) was 44.1% versus 28.6%, with a median progression-free survival of 5.9 versus 6.1 months and median OS of 14.0 versus 12.8 months with VG and VC, respectively.
  
  
  CONCLUSIONS
  Both vinflunine-based doublets offer a similar DCR, ORR and OS. The better haematological tolerance favours the VG combination, which warrants further study. CLINICALTRIALS.GOV PROTOCOL IDENTIFIER: NCT 01599013.
authors.affiliation: Ludwig Boltzmann Institute for ACR VIEnna/LB-CTO ACR-ITR VIEnna, KFJ-Spital, Vienna, Austria Cancer Research Centre, University of Warwick, Coventry, UK maria@desantis.cc.
authors.forename: M
authors.initials: M
authors.lastname: De Santis
authors.affiliation: Oncology Institute, Instytut im Sklodowskiej-Curie, Warsaw, Poland.
authors.forename: P J
authors.initials: PJ
authors.lastname: Wiechno
authors.affiliation: Dana-Farber Cancer Institute-Harvard Medical School, Boston, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France.
authors.forename: C
authors.initials: C
authors.lastname: Lucas
authors.affiliation: Department of Internal Medicine, National Cheng Kung University Hospital, Taipei, Taiwan.
authors.forename: W-C
authors.initials: WC
authors.lastname: Su
authors.affiliation: Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France.
authors.forename: L
authors.initials: L
authors.lastname: Albiges
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Senkus-Konefka
authors.affiliation: Department of Medicine, Centre Léon Bérard, Lyon.
authors.forename: A
authors.initials: A
authors.lastname: Flechon
authors.affiliation: Department of Oncology, Institut Claudius Regaud, Toulouse, France.
authors.forename: L
authors.initials: L
authors.lastname: Mourey
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Department of Urology, KH Barmherzige Schwestern Linz, Linz, Austria.
authors.forename: W C
authors.initials: WC
authors.lastname: Loidl
authors.affiliation: Department of Urology, University Hospital Rechts Der Isar, Munich, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Retz
authors.affiliation: Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France.
authors.forename: N
authors.initials: N
authors.lastname: Vaissière
authors.affiliation: Department of Medical Oncology, Hopital Saint-Louis-APHP, Paris-Diderot University, Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Culine
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; C111217:vinflunine; D014747:Vinblastine; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine
keywords: bladder cancer; cisplatin-ineligible; renal impairment; urothelial carcinoma; vinflunine