title: Randomized phase II/III trial assessing gemcitabine/carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer who are unfit for cisplatin-based chemotherapy: EORTC study 30986.
abstract: OBJECTIVE
  This is the first randomized phase II/III trial comparing two carboplatin-based chemotherapy regimens in patients with urothelial cancer who are ineligible ("unfit") for cisplatin chemotherapy.
  
  
  METHODS
  The primary objective of the phase III part of this study was to compare the overall survival (OS) of chemotherapy-naive patients with measurable disease and an impaired renal function (glomerular filtration rate < 60 but > 30 mL/min) and/or performance score of 2 who were randomly assigned to receive either gemcitabine/carboplatin (GC) or methotrexate/carboplatin/vinblastine (M-CAVI). To detect an increase of 50% in median survival with GC compared with M-CAVI (13.5 v 9 months) based on a two-sided log-rank test at error rates α = .05 and β = .20, 225 patients were required. Secondary end points were overall response rate (ORR), progression-free survival (PFS), toxicity, and quality of life.
  
  
  RESULTS
  In all, 238 patients were randomly assigned by 29 institutions over a period of 7 years. The median follow-up was 4.5 years. Best ORRs were 41.2% (36.1% confirmed response) for patients receiving GC versus 30.3% (21.0% confirmed response) for patients receiving M-CAVI (P = .08). Median OS was 9.3 months in the GC arm and 8.1 months in the M-CAVI arm (P = .64). There was no difference in PFS (P = .78) between the two arms. Severe acute toxicity (death, grade 4 thrombocytopenia with bleeding, grade 3 or 4 renal toxicity, neutropenic fever, or mucositis) was observed in 9.3% of patients receiving GC and 21.2% of patients receiving M-CAVI.
  
  
  CONCLUSIONS
  There were no significant differences in efficacy between the two treatment groups. The incidence of severe acute toxicities was higher for those receiving M-CAVI.
authors.affiliation: Kaiser Franz Josef Hospital and ACR-ITR Vienna/CEADDP and LBI-ACR Vienna-CTO, Kundratstraße 3,Vienna, Austria 1100. maria.desantis@wienkav.at
authors.forename: Maria
authors.initials: M
authors.lastname: De Santis
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Graham
authors.initials: G
authors.lastname: Mead
authors.forename: J Martijn
authors.initials: JM
authors.lastname: Kerst
authors.forename: Michael
authors.initials: M
authors.lastname: Leahy
authors.forename: Pablo
authors.initials: P
authors.lastname: Maroto
authors.forename: Thierry
authors.initials: T
authors.lastname: Gil
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.forename: Iwona
authors.initials: I
authors.lastname: Skoneczna
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Julie
authors.initials: J
authors.lastname: Lorent
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002945:Cisplatin; D000075202:Contraindications; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011788:Quality of Life; D011795:Surveys and Questionnaires; D015996:Survival Rate; D014571:Urologic Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D014747:Vinblastine; D016190:Carboplatin; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine