title: Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy: EORTC Intergroup Study 30987.
abstract: OBJECTIVE
  The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival.
  
  
  METHODS
  We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity.
  
  
  RESULTS
  From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001).
  
  
  CONCLUSIONS
  The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.
authors.affiliation: Vall d’Hebron University Hospital, Barcelona, Spain. jbellmunt@parcdesalutmar.cat
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
authors.forename: Graham M
authors.initials: GM
authors.lastname: Mead
authors.forename: Iwona
authors.initials: I
authors.lastname: Skoneczna
authors.forename: Maria
authors.initials: M
authors.lastname: De Santis
authors.forename: Gedske
authors.initials: G
authors.lastname: Daugaard
authors.forename: Andreas
authors.initials: A
authors.lastname: Boehle
authors.forename: Christine
authors.initials: C
authors.lastname: Chevreau
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Laufman
authors.forename: Eric
authors.initials: E
authors.lastname: Winquist
authors.forename: Derek
authors.initials: D
authors.lastname: Raghavan
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marreaud
authors.forename: Sandra
authors.initials: S
authors.lastname: Collette
authors.forename: Richard
authors.initials: R
authors.lastname: Sylvester
authors.forename: Ronald
authors.initials: R
authors.lastname: de Wit
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine