title: Cediranib monotherapy in patients with advanced renal cell carcinoma: results of a randomised phase II study.
abstract: BACKGROUND
  Cediranib is a highly potent vascular endothelial growth factor (VEGF) signalling inhibitor with activity against VEGF receptors 1, 2 and 3. This Phase II, randomised, double-blind, parallel-group study compared the efficacy of cediranib with placebo in patients with metastatic or recurrent clear cell renal cell carcinoma who had not previously received a VEGF signalling inhibitor.
  
  
  METHODS
  Patients were randomised (3:1) to cediranib 45 mg/day or placebo. The primary objective was comparison of change from baseline in tumour size after 12 weeks of therapy. Secondary objectives included response rate and duration, progression-free survival (PFS) and safety and tolerability. Patients in the placebo group could cross over to open-label cediranib at 12 weeks or earlier if their disease had progressed. This study has been completed and is registered with ClinicalTrials.gov, number NCT00423332.
  
  
  RESULTS
  Patients (n=71) were randomised to receive cediranib (n=53) or placebo (n=18). The primary study outcome revealed that, after 12weeks of therapy, there was a significant difference in mean percentage change from baseline in tumour size between the cediranib (-20%) and placebo (+20%) arms (p<0.0001). Eighteen patients (34%) on cediranib achieved a partial response and 25 (47%) experienced stable disease. Cediranib treatment prolonged PFS significantly compared with placebo (hazard ratio (HR)=0.45, 90%confidence interval: 0.26-0.76, p=0.017; median PFS 12.1 versus 2.8 months). The most common adverse events in patients receiving cediranib were diarrhoea (74%), hypertension (64%), fatigue (58%) and dysphonia (58%).
  
  
  CONCLUSIONS
  Cediranib monotherapy demonstrated significant evidence of antitumour activity in patients with advanced renal cell carcinoma. The adverse event profile was consistent with previous studies of cediranib 45 mg.
authors.affiliation: Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. p.mulders@uro.umcn.nl
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.forename: Robert
authors.initials: R
authors.lastname: Hawkins
authors.forename: Paul
authors.initials: P
authors.lastname: Nathan
authors.forename: Igle
authors.initials: I
authors.lastname: de Jong
authors.forename: Susanne
authors.initials: S
authors.lastname: Osanto
authors.forename: Emilio
authors.initials: E
authors.lastname: Porfiri
authors.forename: Andrew
authors.initials: A
authors.lastname: Protheroe
authors.forename: Carla M L
authors.initials: CM
authors.lastname: van Herpen
authors.forename: Bijoyesh
authors.initials: B
authors.lastname: Mookerjee
authors.forename: Laura
authors.initials: L
authors.lastname: Pike
authors.forename: Juliane M
authors.initials: JM
authors.lastname: Jürgensmeier
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gore
mesh_terms: D000368:Aged; D000465:Algorithms; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011799:Quinazolines / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D011799:Quinazolines; C500926:cediranib; D007211:Indoles