PMID- 26673352 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20221207 IS - 1569-8041 (Electronic) IS - 0923-7534 (Print) IS - 0923-7534 (Linking) VI - 27 IP - 3 DP - 2016 Mar TI - 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). PG - 449-54 LID - 10.1093/annonc/mdv609 [doi] AB - 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. PATIENTS AND 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 (alpha = 5%, beta = 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. CONCLUSION: 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. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. FAU - De Santis, M AU - De Santis M AD - 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. FAU - Wiechno, P J AU - Wiechno PJ AD - Oncology Institute, Instytut im Sklodowskiej-Curie, Warsaw, Poland. FAU - Bellmunt, J AU - Bellmunt J AD - Dana-Farber Cancer Institute-Harvard Medical School, Boston, USA. FAU - Lucas, C AU - Lucas C AD - Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France. FAU - Su, W-C AU - Su WC AD - Department of Internal Medicine, National Cheng Kung University Hospital, Taipei, Taiwan. FAU - Albiges, L AU - Albiges L AD - Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France. FAU - Lin, C-C AU - Lin CC AD - Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. FAU - Senkus-Konefka, E AU - Senkus-Konefka E AD - Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland. FAU - Flechon, A AU - Flechon A AD - Department of Medicine, Centre Leon Berard, Lyon. FAU - Mourey, L AU - Mourey L AD - Department of Oncology, Institut Claudius Regaud, Toulouse, France. FAU - Necchi, A AU - Necchi A AD - Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. FAU - Loidl, W C AU - Loidl WC AD - Department of Urology, KH Barmherzige Schwestern Linz, Linz, Austria. FAU - Retz, M M AU - Retz MM AD - Department of Urology, University Hospital Rechts Der Isar, Munich, Germany. FAU - Vaissiere, N AU - Vaissiere N AD - Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France. FAU - Culine, S AU - Culine S AD - Department of Medical Oncology, Hopital Saint-Louis-APHP, Paris-Diderot University, Paris, France. LA - eng SI - ClinicalTrials.gov/NCT01599013 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20151216 PL - England TA - Ann Oncol JT - Annals of oncology : official journal of the European Society for Medical Oncology JID - 9007735 RN - 0W860991D6 (Deoxycytidine) RN - 5BF646324K (vinflunine) RN - 5V9KLZ54CY (Vinblastine) RN - BG3F62OND5 (Carboplatin) RN - Q20Q21Q62J (Cisplatin) RN - 0 (Gemcitabine) SB - IM CIN - Eur Urol. 2016 Aug;70(2):399-400. PMID: 27353965 MH - Adult MH - Aged MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/adverse effects/*therapeutic use MH - Carcinoma, Transitional Cell/*drug therapy MH - Cisplatin/therapeutic use MH - Deoxycytidine/adverse effects/*analogs & derivatives/therapeutic use MH - Disease-Free Survival MH - Female MH - Humans MH - Male MH - Middle Aged MH - Treatment Outcome MH - Urinary Bladder Neoplasms/*drug therapy MH - Vinblastine/adverse effects/*analogs & derivatives/therapeutic use MH - Gemcitabine PMC - PMC4769994 OTO - NOTNLM OT - bladder cancer OT - cisplatin-ineligible OT - renal impairment OT - urothelial carcinoma OT - vinflunine EDAT- 2015/12/18 06:00 MHDA- 2016/12/15 06:00 PMCR- 2015/12/16 CRDT- 2015/12/18 06:00 PHST- 2015/08/10 00:00 [received] PHST- 2015/12/05 00:00 [accepted] PHST- 2015/12/18 06:00 [entrez] PHST- 2015/12/18 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] PHST- 2015/12/16 00:00 [pmc-release] AID - S0923-7534(19)35603-0 [pii] AID - mdv609 [pii] AID - 10.1093/annonc/mdv609 [doi] PST - ppublish SO - Ann Oncol. 2016 Mar;27(3):449-54. doi: 10.1093/annonc/mdv609. Epub 2015 Dec 16.