title: Impact of the number of prior lines of therapy and prior perioperative chemotherapy in patients receiving salvage therapy for advanced urothelial carcinoma: implications for trial design.
abstract: BACKGROUND
  The differential impact of the number of prior lines of therapy and the setting of prior therapy (perioperative or metastatic) is unclear in advanced urothelial carcinoma.
  
  
  METHODS
  Ten phase II trials of salvage chemotherapy, biologic agent therapy, or both, enrolling 731 patients, were available. Data on the number of prior lines of therapy and the setting of prior therapy were required in addition to known previously recognized prognostic factors: time from prior chemotherapy, hemoglobin level, performance status, and liver metastasis status. Cox proportional hazards regression was used to evaluate the association of the number of prior lines and prior perioperative therapy with overall survival (OS) as the primary clinical endpoint. Trial was a stratification factor.
  
  
  RESULTS
  A total of 711 patients were evaluable. The overall median progression-free survival and OS were 2.7 and 6.8 months, respectively. The number of prior lines was 1 in 559 patients (78.6%), 2 in 111 (15.6%), 3 in 29 (4.1%), 4 in 10 (1.4%), and 5 in 2 (0.3%). Prior perioperative chemotherapy was given to 277 (39.1%) and chemotherapy for metastatic disease to 454 (64.1%). The number of prior lines was not independently associated with OS (hazard ratio, 0.99; 95% CI, 0.86-1.14). Prior perioperative chemotherapy was a favorable factor for OS on univariate but not multivariate analysis.
  
  
  CONCLUSIONS
  The number of prior lines of therapy and prior perioperative chemotherapy were not independently prognostic in patients with urothelial carcinoma receiving salvage therapy. Adoption of these data in salvage therapy trials should enhance accrual, the interpretability of results, and drug development.
authors.affiliation: McMaster University, Hamilton, ON.
authors.forename: G R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: University Hospital del Mar, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: J E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: D F
authors.initials: DF
authors.lastname: Bajorin
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: A M
authors.initials: AM
authors.lastname: Regazzi
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: T K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
authors.forename: A Q
authors.initials: AQ
authors.lastname: Qu
authors.affiliation: Heinrich Heine University, Dusseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Niegisch
authors.affiliation: Heinrich Heine University, Dusseldorf, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Albers
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Necchi
authors.affiliation: University Federico II, Naples, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Institut de Recherche Pierre Fabre, Boulogne, France.
authors.forename: R
authors.initials: R
authors.lastname: Fougeray
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Y-N
authors.initials: YN
authors.lastname: Wong
authors.affiliation: Princess Margaret Hospital, Toronto, ON.
authors.forename: S S
authors.initials: SS
authors.lastname: Sridhar
authors.affiliation: Sunnybrook Odette Cancer Centre, Toronto, ON.
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Ko
authors.affiliation: University of North Carolina, Chapel Hill, NC.
authors.forename: M I
authors.initials: MI
authors.lastname: Milowsky
authors.affiliation: Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY.
authors.forename: M D
authors.initials: MD
authors.lastname: Galsky
authors.affiliation: University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
authors.forename: G
authors.initials: G
authors.lastname: Sonpavde
mesh_terms: D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D004358:Drug Therapy / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D019990:Perioperative Care; D011446:Prospective Studies; D012044:Regression Analysis; D016879:Salvage Therapy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality*
keywords: Advanced; Number of prior regimens; Prior perioperative chemotherapy; Prognosis; Salvage therapy; Urothelial carcinoma