title: Incomplete Cross-Resistance Between Taxanes for Advanced Urothelial Carcinoma: Implications for Clinical Practice and Trial Design.
abstract: BACKGROUND
  Taxanes such as paclitaxel and docetaxel are commonly used for second- or third-line salvage systemic therapy for metastatic UC. Although trials have generally excluded previous exposure to taxanes when using a taxane in a salvage therapy trial, taxanes might not be completely cross-resistant. Hence, we aimed to study outcomes with docetaxel after previous paclitaxel and the reverse sequence, to identify the level of cross-resistance between these taxanes.
  
  
  METHODS
  Data from a randomized phase II trial that compared salvage therapy with docetaxel combined with either placebo or vandetanib for advanced UC were analyzed. Both arms were combined for analysis because no differences in any outcomes were observed. Data were also requested from institutions for patients who received paclitaxel after previous docetaxel treatment. Descriptive statistics were used to summarize patient and treatment characteristics and outcomes. The primary clinical end point of interest was overall survival (OS).
  
  
  RESULTS
  Of 148 patients who received docetaxel with either vandetanib or placebo, 21 had received previous paclitaxel treatment. No difference in OS, progression-free survival, or response rate was observed with docetaxel based on previous paclitaxel treatment after adjusting for known prognostic factors. Among the 8 patients who received paclitaxel after previous docetaxel treatment, partial response was observed in 1 patient (12.5%) and stable disease in 2 patients (25%).
  
  
  CONCLUSIONS
  Docetaxel treatment after previous paclitaxel treatment and the reverse sequence demonstrates activity in advanced UC. There is no strong evidence to disallow patients with previous exposure to a taxane to enroll in a clinical trial involving another taxane.
authors.affiliation: University of Alabama, Birmingham (UAB) Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: McMaster University, Hamilton, Ontario, Canada.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Pond
authors.affiliation: Dana Farber Cancer Institute, Boston, MA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Mullane
authors.affiliation: Dana Farber Cancer Institute, Boston, MA.
authors.forename: Angela Q
authors.initials: AQ
authors.lastname: Qu
authors.affiliation: University Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Lorenzo
authors.affiliation: Istituto Ospedaliero del Sud (IOS) and Coleman, Napoli, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Federico
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Dana Farber Cancer Institute, Boston, MA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Dana Farber Cancer Institute, Boston, MA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
mesh_terms: D000368:Aged; D017322:Clinical Trials, Phase II as Topic; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: D010880:Piperidines; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; C452423:vandetanib
keywords: Docetaxel; Paclitaxel; Prognosis; Salvage therapy; Urothelial carcinoma