title: Cediranib with mFOLFOX6 vs bevacizumab with mFOLFOX6 in previously treated metastatic colorectal cancer.
abstract: BACKGROUND
  Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC).
  
  
  METHODS
  Patients with mCRC who had progressed following first-line therapy were randomised 1:1:1 to modified (m)FOLFOX6 plus cediranib (20 or 30 mg day(-1)) or bevacizumab (10 mg kg(-1) every 2 weeks). The primary objective was to compare progression-free survival (PFS) between treatment arms.
  
  
  RESULTS
  A total of 210 patients were included in the intent-to-treat (ITT) analysis (cediranib 20 mg, n=71; cediranib 30 mg, n=73; bevacizumab, n=66). Median PFS in the cediranib 20 mg, cediranib 30 mg and bevacizumab groups was 5.8, 7.2 and 7.8 months, respectively. There were no statistically significant differences between treatment arms for PFS (cediranib 20 mg vs bevacizumab: HR=1.28 (95% CI, 0.85-1.95; P=0.29); cediranib 30 mg vs bevacizumab: HR=1.17 (95% CI, 0.77-1.76; P=0.79)) or overall survival (OS). Grade ≥ 3 adverse events were more common with cediranib 30 mg (91.8%) vs cediranib 20 mg (81.4%) or bevacizumab (84.8%).
  
  
  CONCLUSIONS
  There were no statistically significant differences between treatment arms for PFS or OS. When combined with mFOLFOX6, the 20 mg day(-1) dose of cediranib was better tolerated than the 30 mg day(-1) dose.
authors.affiliation: Medical Oncology, Royal Marsden Hospital, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. David.Cunningham@rmh.nhs.uk
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: R P W
authors.initials: RP
authors.lastname: Wong
authors.forename: G
authors.initials: G
authors.lastname: D'Haens
authors.forename: J-Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: J
authors.initials: J
authors.lastname: Robertson
authors.forename: A M
authors.initials: AM
authors.lastname: Stone
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007390:International Agencies; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage; D016879:Salvage Therapy; D015996:Survival Rate; D055815:Young Adult; D007211:Indoles
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D011799:Quinazolines; C500926:cediranib; D007211:Indoles