title: Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer.
abstract: BACKGROUND
  Cediranib is a potent oral vascular endothelial growth factor (VEGF) signalling inhibitor with activity against all three VEGF receptors. The International Collaboration for Ovarian Neoplasia 6 (ICON6) trial was initiated based on evidence of single-agent activity in ovarian cancer with acceptable toxicity.
  
  
  METHODS
  The ICON6 trial is a 3-arm, 3-stage, double-blind, placebo-controlled randomised trial in first relapse of platinum-sensitive ovarian cancer. Patients are randomised (2 : 3 : 3) to receive six cycles of carboplatin (AUC5/6) plus paclitaxel (175 mg m(-2)) with either placebo (reference), cediranib 20 mg per day, followed by placebo (concurrent), or cediranib 20 mg per day, followed by cediranib (concurrent plus maintenance). Cediranib or placebo was continued for 18 months or until disease progression. The primary outcome measure for stage I was safety, and the blinded results are presented here.
  
  
  RESULTS
  Sixty patients were included in the stage I analysis. A total of 53 patients had received three cycles of chemotherapy and 42 patients had completed six cycles. In all, 19 out of 60 patients discontinued cediranib or placebo during chemotherapy because of adverse events/intercurrent illness (n=9); disease progression (n=1); death (n=3); patient decision (n=1); administrative reasons (n=1); and multiple reasons (n=4). Grade 3 and 4 toxicity was experienced by 30 (50%) and 3 (5%) patients, respectively. No gastrointestinal perforations were observed.
  
  
  CONCLUSIONS
  The addition of cediranib to platinum-based chemotherapy is sufficiently well tolerated to expand the ICON6 trial and progress to stage II.
authors: Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, University College London, 90 Tottenham Court Road, London W1T 4TJ, UK.
authors: F A
authors: FA
authors: Raja
authors: C L
authors: CL
authors: Griffin
authors: W
authors: W
authors: Qian
authors: H
authors: H
authors: Hirte
authors: M K
authors: MK
authors: Parmar
authors: A M
authors: AM
authors: Swart
authors: J A
authors: JA
authors: Ledermann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D000077216:Carcinoma, Ovarian Epithelial; D002945:Cisplatin / Q000008:administration & dosage; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D007211:Indoles
chemical_list: D016190:Carboplatin; D002945:Cisplatin; D017239:Paclitaxel; D011799:Quinazolines; C500926:cediranib; D007211:Indoles