title: Phase II clinical trial of cediranib in patients with metastatic castration-resistant prostate cancer.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of cediranib, a highly potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, in patients with metastatic castration-resistant prostate cancer (CRPC) previously treated with docetaxel-based therapy.
  
  
  METHODS
  The study used a Simon two-stage trial design, which required at least two of 12 patients in the first cohort to be progression-free at 6 months. We enrolled a total of 35 evaluable patients who all received cediranib 20 mg orally daily. In a second cohort, 23 additional patients received prednisone 10 mg daily with cediranib. Endpoints included tumour response, progression-free survival (PFS), overall survival (OS), vascular permeability via dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and toxicity.
  
  
  RESULTS
  A total of 59 patients were enrolled, of whom 67% had received two or more previous chemotherapy regimens. Six of 39 patients with measurable disease had confirmed partial responses and one had an unconfirmed partial response. At 6 months, 43.9% of patients were progression-free; the median PFS and OS periods for all patients were 3.7 months and 10.1 months, respectively. We found that the DCE-MRI variables baseline transport constant (Ktrans ) and rate constant at day 28 were significantly associated with PFS in univariate analyses, but only baseline Ktrans remained significant when considered jointly. The most frequent toxicities were hypertension, fatigue, anorexia and weight loss; the addition of prednisone reduced the incidence of constitutional toxicities.
  
  
  CONCLUSIONS
  This study demonstrated that cediranib was generally well tolerated with some anti-tumour activity in highly pretreated patients with metastatic CRPC who had progressive disease after docetaxel-based therapy.
authors: Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
authors: William L
authors: WL
authors: Dahut
authors: Ravi A
authors: RA
authors: Madan
authors: Joyson J
authors: JJ
authors: Karakunnel
authors: David
authors: D
authors: Adelberg
authors: James L
authors: JL
authors: Gulley
authors: Ismail B
authors: IB
authors: Turkbey
authors: Cindy H
authors: CH
authors: Chau
authors: Shawn D
authors: SD
authors: Spencer
authors: Marcia
authors: M
authors: Mulquin
authors: John
authors: J
authors: Wright
authors: Howard L
authors: HL
authors: Parnes
authors: Seth M
authors: SM
authors: Steinberg
authors: Peter L
authors: PL
authors: Choyke
authors: William D
authors: WD
authors: Figg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000284:Administration, Oral; D000368:Aged; D004305:Dose-Response Relationship, Drug; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D007211:Indoles
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C500926:cediranib; D007211:Indoles