title: Double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated metastatic urothelial cancer.
abstract: OBJECTIVE
  Vandetanib is an oral once-daily tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 and epidermal growth factor receptor. Vandetanib in combination with docetaxel was assessed in patients with advanced urothelial cancer (UC) who progressed on prior platinum-based chemotherapy.
  
  
  METHODS
  The primary objective was to determine whether vandetanib 100 mg plus docetaxel 75 mg/m(2) intravenously every 21 days prolonged progression-free survival (PFS) versus placebo plus docetaxel. The study was designed to detect a 60% improvement in median PFS with 80% power and one-sided α at 5%. Patients receiving docetaxel plus placebo had the option to cross over to single-agent vandetanib at progression. Overall survival (OS), overall response rate (ORR), and safety were secondary objectives.
  
  
  RESULTS
  In all, 142 patients were randomly assigned and received at least one dose of therapy. Median PFS was 2.56 months for the docetaxel plus vandetanib arm versus 1.58 months for the docetaxel plus placebo arm, and the hazard ratio for PFS was 1.02 (95% CI, 0.69 to 1.49; P = .9). ORR and OS were not different between both arms. Grade 3 or higher toxicities were more commonly seen in the docetaxel plus vandetanib arm and included rash/photosensitivity (11% v 0%) and diarrhea (7% v 0%). Among 37 patients who crossed over to single-agent vandetanib, ORR was 3% and OS was 5.2 months.
  
  
  CONCLUSIONS
  In this platinum-pretreated population of advanced UC, the addition of vandetanib to docetaxel did not result in a significant improvement in PFS, ORR, or OS. The toxicity of vandetanib plus docetaxel was greater than that for vendetanib plus placebo. Single-agent vandetanib activity was minimal.
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA 02215, USA. Toni_Choueiri@dfci.harvard.edu
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.forename: Robert W
authors.initials: RW
authors.lastname: Ross
authors.forename: Susanna
authors.initials: S
authors.lastname: Jacobus
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Yu
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Noah M
authors.initials: NM
authors.lastname: Hahn
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Hutson
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Morrissey
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Buckle
authors.forename: William Y
authors.initials: WY
authors.lastname: Kim
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Ryan
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Amir
authors.initials: A
authors.lastname: Mortazavi
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Bubley
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.forename: Philip W
authors.initials: PW
authors.lastname: Kantoff
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D018572:Disease-Free Survival; D000077143:Docetaxel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects; D017671:Platinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D016016:Proportional Hazards Models; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D017211:Treatment Failure; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology*
chemical_list: D010880:Piperidines; D017671:Platinum Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D043823:Taxoids; D000077143:Docetaxel; D011505:Protein-Tyrosine Kinases; C452423:vandetanib