title: A phase II safety and efficacy study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer.
abstract: BACKGROUND
  Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma.
  
  
  METHODS
  Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle.
  
  
  RESULTS
  Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed.
  
  
  CONCLUSIONS
  Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies.
authors.affiliation: Roswell Park Cancer Institute, Buffalo, NY. Electronic address: Roberto.Pili@RoswellPark.org.
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Rui
authors.initials: R
authors.lastname: Qin
authors.forename: P J
authors.initials: PJ
authors.lastname: Flynn
authors.forename: Joel
authors.initials: J
authors.lastname: Picus
authors.forename: Michael
authors.initials: M
authors.lastname: Millward
authors.forename: Wing Ming
authors.initials: WM
authors.lastname: Ho
authors.forename: Henry
authors.initials: H
authors.lastname: Pitot
authors.forename: Winston
authors.initials: W
authors.lastname: Tan
authors.forename: Kiersten M
authors.initials: KM
authors.lastname: Miles
authors.forename: Charles
authors.initials: C
authors.lastname: Erlichman
authors.forename: Ulka
authors.initials: U
authors.lastname: Vaishampayan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Pazopanib; Urothelial cancer; VEGF tyrosine kinase inhibitors
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