title: A phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer: a trial of the Princess Margaret, Chicago and California Phase II Consortia.
abstract: OBJECTIVE
  Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC).
  
  
  METHODS
  Eligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45mg to 30mg. The primary endpoint was objective response rate at 16weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R).
  
  
  RESULTS
  74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58years [31-87]. In PL-S group, 10 (26%) partial responses (PR) and 20 (51%) stable disease (SD) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities observed at the 30 mg starting dose were hypertension (27%), fatigue (20%) and diarrhea (14%). The median progression-free survival for all patients was 4.9months [3.9-7.0], 7.2months [4.3-9] for PL-S and 3.7months [2.6-4.5] for PL-R groups. The median overall survival was 18.9months (95% CI: 13.5-31.5); 27.7months [17.8-43.3] for PL-S and 11.9months [8.1-18.9] for PL-R groups.
  
  
  CONCLUSIONS
  Cediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30mg od.
authors.affiliation: Juravinski Cancer Centre, Hamilton, ON, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Hirte
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Lheureux
authors.affiliation: The University of Chicago Medical Center, Chicago, IL, United States.
authors.forename: G F
authors.initials: GF
authors.lastname: Fleming
authors.affiliation: London Health Sciences Centre, London, ON, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Sugimoto
authors.affiliation: City of Hope Medical Center, Duarte, CA, United States.
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.affiliation: Cancer Centre of Southeastern Ontario, Kingston, ON, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Biagi
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada.
authors.forename: S
authors.initials: S
authors.lastname: McGill
authors.affiliation: National Cancer Institute, Bethesda, MD, United States.
authors.forename: S P
authors.initials: SP
authors.lastname: Ivy
authors.affiliation: Princess Margaret Cancer Centre, Toronto, ON, Canada. Electronic address: amit.oza@uhn.ca.
authors.forename: A M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
keywords: Cediranib; Ovarian cancer; Phase 2; Recurrence