title: Cediranib in combination with mFOLFOX6 in Japanese patients with metastatic colorectal cancer: results from the randomised phase II part of a phase I/II study.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the second most common malignancy in Japan. Treatment with inhibitors of the vascular endothelial growth factor (VEGF) signalling pathway has proven benefit in metastatic CRC. Cediranib is an oral highly potent VEGF signalling inhibitor that inhibits all three VEGF receptors.
  
  
  METHODS
  In this phase II, double-blind, placebo-controlled study, 172 patients with metastatic CRC were randomised to receive once-daily cediranib (20 or 30 mg) or placebo, each combined with modified FOLFOX6 (mFOLFOX6). The primary objective was comparison of progression-free survival (PFS).
  
  
  RESULTS
  The comparison of cediranib 20 mg versus placebo met the primary objective of PFS prolongation [hazard ratio = 0.70 (95% confidence interval 0.44-1.11), P = 0.167], which met the protocol-defined criterion of P < 0.2. Median PFS was 10.2 versus 8.3 months, respectively. The PFS comparison for cediranib 30 mg versus placebo did not meet the criterion. The most common adverse events (AEs) in the cediranib-containing groups were diarrhoea and hypertension.
  
  
  CONCLUSIONS
  Cediranib 20 mg plus mFOLFOX6 met the predefined criteria in terms of improved PFS compared with placebo plus mFOLFOX6. Cediranib 20 mg was generally well tolerated and the AE profile was consistent with previous studies.
authors.affiliation: Department of Surgery, Minoh City Hospital, Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Muro
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Bando
authors.forename: S
authors.initials: S
authors.lastname: Hazama
authors.forename: K
authors.initials: K
authors.lastname: Amagai
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.forename: T
authors.initials: T
authors.lastname: Denda
authors.forename: X
authors.initials: X
authors.lastname: Shi
authors.forename: K
authors.initials: K
authors.lastname: Fukase
authors.forename: J
authors.initials: J
authors.lastname: Skamoto
authors.forename: H
authors.initials: H
authors.lastname: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D015179:Colorectal Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D007211:Indoles
chemical_list: D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D011799:Quinazolines; D042461:Vascular Endothelial Growth Factor A; C500926:cediranib; D007211:Indoles