title: A randomized, phase II study of pazopanib in castrate-sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study.
abstract: BACKGROUND
  Intermittent androgen suppression (IAS) is an increasingly popular treatment option for castrate-sensitive prostate cancer. On the basis of previous data with anti-angiogenic strategies, we hypothesized that pan-inhibition of the vascular endothelial growth factor receptor using pazopanib during the IAS off period would result in prolonged time to PSA failure.
  
  
  METHODS
  Men with biochemically recurrent prostate cancer, whose PSA was <0.5 ng ml(-1) after 6 months of androgen deprivation therapy were randomized to pazopanib 800 mg daily or observation. The planned primary outcome was time to PSA progression >4.0 ng ml(-1).
  
  
  RESULTS
  Thirty-seven patients were randomized. Of 18 patients randomized to pazopanib, at the time of study closure, 4 had progressive disease, 1 remained on treatment and 13 (72%) electively disenrolled, the most common reason being patient request due to grade 1/2 toxicity (8 patients). Two additional patients were removed from treatment due to adverse events. Of 19 patients randomized to observation, at the time of study closure, 4 had progressive disease, 7 remained under protocol-defined observation and 8 (42%) had disenrolled, most commonly due to non-compliance with protocol visits (3 patients). Because of high dropout rates in both arms, the study was halted.
  
  
  CONCLUSIONS
  IAS is a treatment approach that may facilitate investigation of novel agents in the hormone-sensitive state. This trial attempted to investigate the role of antiangiogenic therapy in this setting, but encountered several barriers, including toxicities and patient non-compliance, which can make implementation of such a study difficult. Future investigative efforts in this arena should carefully consider drug toxicity and employ a design that maximizes patient convenience to reduce the dropout rate.
authors: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors: J E
authors: JE
authors: Ward
authors: T
authors: T
authors: Karrison
authors: G
authors: G
authors: Chatta
authors: M
authors: M
authors: Hussain
authors: D
authors: D
authors: Shevrin
authors: R Z
authors: RZ
authors: Szmulewitz
authors: P H
authors: PH
authors: O'Donnell
authors: W M
authors: WM
authors: Stadler
authors: E M
authors: EM
authors: Posadas
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002641:Chicago; D003967:Diarrhea / Q000139:chemically induced; D057239:Early Termination of Clinical Trials; D005221:Fatigue / Q000139:chemically induced; D006801:Humans; D007191:Indazoles; D008297:Male; D009919:Orchiectomy; D010349:Patient Compliance; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D059030:United States Department of Defense; D014495:Universities
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib