title: Cediranib, an oral inhibitor of vascular endothelial growth factor receptor kinases, is an active drug in recurrent epithelial ovarian, fallopian tube, and peritoneal cancer.
abstract: OBJECTIVE
  Angiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR) -1, VEGFR-2, VEGFR-3, and c-kit.
  
  
  METHODS
  We conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included <or= two lines of chemotherapy for recurrence. End points included response rate (via Response Evaluation Criteria in Solid Tumors [RECIST] or modified Gynecological Cancer Intergroup CA-125), toxicity, progression-free survival (PFS), and overall survival (OS).
  
  
  RESULTS
  Forty-seven patients were enrolled; 46 were treated. Clinical benefit rate (defined as complete response [CR] or partial response [PR], stable disease [SD] > 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months.
  
  
  CONCLUSIONS
  Cediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, MA 02115, USA. Ursula_matulonis@dfci.harvard.edu
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
authors.forename: Suzanne
authors.initials: S
authors.lastname: Berlin
authors.forename: Percy
authors.initials: P
authors.lastname: Ivy
authors.forename: Karin
authors.initials: K
authors.lastname: Tyburski
authors.forename: Carolyn
authors.initials: C
authors.lastname: Krasner
authors.forename: Corrine
authors.initials: C
authors.lastname: Zarwan
authors.forename: Anna
authors.initials: A
authors.lastname: Berkenblit
authors.forename: Susana
authors.initials: S
authors.lastname: Campos
authors.forename: Neil
authors.initials: N
authors.lastname: Horowitz
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Cannistra
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.forename: Julie
authors.initials: J
authors.lastname: Lee
authors.forename: Maria
authors.initials: M
authors.lastname: Roche
authors.forename: Margaret
authors.initials: M
authors.lastname: Hill
authors.forename: Christin
authors.initials: C
authors.lastname: Whalen
authors.forename: Laura
authors.initials: L
authors.lastname: Sullivan
authors.forename: Chau
authors.initials: C
authors.lastname: Tran
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Humphreys
authors.forename: Richard T
authors.initials: RT
authors.lastname: Penson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D007211:Indoles
chemical_list: D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; C500926:cediranib; D007211:Indoles