title: Pooled analysis of phase II trials evaluating weekly or conventional cisplatin as first-line therapy for advanced urothelial carcinoma.
abstract: BACKGROUND
  Weekly gemcitabine with GC every 3-4 weeks is considered conventional first-line chemotherapy for advanced urothelial carcinoma (UC). Weekly split-dose cisplatin with wGC might be less toxic and have similar activity, but has not been compared with GC. We pooled published phase II trials of GC and wGC to compare efficacy and safety.
  
  
  METHODS
  Two trials of wGC and 3 trials of GC were identified. Because the data were not derived from randomized trials, GC and wGC were not formally compared, and exact 95% quasi-binomial confidence intervals (CI), for response rates and grade ≥ 3 toxicities were calculated.
  
  
  RESULTS
  The 95% CI overlapped, suggesting agreement between wGC and GC. No clear difference in response rates and grade ≥ 3 toxicities between GC and wGC were observed.
  
  
  CONCLUSIONS
  Gemcitabine combined with day 1 cisplatin and wGC yielded similar responses and grade ≥ 3 toxicities in advanced UC in a hypothesis-generating pooled analysis of phase II trials. Considering the probable lower nephrotoxicity of fractionated cisplatin, prospective evaluation of wGC might be warranted across cisplatin-eligible and -ineligible patients to develop a single chemotherapy template for the development of combinations with biological agents in a broad population of patients.
authors: University of Utah, Huntsman Cancer Institute, Salt Lake City, UT, USA.
authors: Benjamin L
authors: BL
authors: Maughan
authors: Neeraj
authors: N
authors: Agarwal
authors: Syed A
authors: SA
authors: Hussain
authors: Kenneth M
authors: KM
authors: Boucher
authors: Hans
authors: H
authors: Von Der Maase
authors: Donald S
authors: DS
authors: Kaufman
authors: Vito
authors: V
authors: Lorusso
authors: Malcolm J
authors: MJ
authors: Moore
authors: Matthew D
authors: MD
authors: Galsky
authors: Guru
authors: G
authors: Sonpavde
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D019459:Urothelium / Q000187:drug effects / Q000473:pathology; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Advanced urothelial carcinoma; Cisplatin; Conventional; Fractionated; Response rate; Toxicities; Weekly