title: A phase II evaluation of cediranib in the treatment of recurrent or persistent endometrial cancer: An NRG Oncology/Gynecologic Oncology Group study.
abstract: OBJECTIVE
  Cediranib is a multi-tyrosine kinase inhibitor targeting vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF) receptors. This phase II study was conducted to assess activity and tolerability of single-agent cediranib in recurrent/persistent endometrial cancer.
  
  
  METHODS
  Eligible patients had recurrent or persistent endometrial cancer after receiving one or two prior cytotoxic regimens, measurable disease, and Gynecologic Oncology Group (GOG) performance status of ≤2 (≤1 if two prior cytotoxic regimens given). Cediranib 30mg orally daily for a 28daycycle was administered until disease progression or prohibitive toxicity. Microvessel density (MVD) was measured in tumor tissue from initial hysterectomy specimens and correlated with clinical outcome. Primary endpoints were tumor response and surviving progression-free for six months without subsequent therapy (6-month event-free survival [EFS]).
  
  
  RESULTS
  Of 53 patients enrolled, 48 were evaluable for cediranib efficacy and toxicity. Median age was 65.5 years, 52% of patients had received prior radiation, and 73% of patients received only one prior chemotherapy regimen. A partial response was observed in 12.5%. Fourteen patients (29%) had six-month EFS. Median progression-free survival (PFS) was 3.65 months and median overall survival (OS) 12.5 months. No grade 4 or 5 toxicities were observed. A trend towards improved PFS was found in patients whose tumors expressed high MVD.
  
  
  CONCLUSIONS
  Cediranib as a monotherapy treatment for recurrent or persistent endometrial cancer is well tolerated and met protocol set objectives for sufficient activity to warrant further investigation. MVD may be a useful biomarker for activity.
authors.affiliation: Gynecologic Oncology Division, University of Iowa, Gyn/Onc Division, Iowa City, IA 52242, United States. Electronic address: david-bender@uiowa.edu.
authors.forename: David
authors.initials: D
authors.lastname: Bender
authors.affiliation: NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: msill@gogstats.org.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Sill
authors.affiliation: NRG Oncology Statistics & Data Management Center, Roswell Park Cancer Institute, Buffalo, NY 14263, United States. Electronic address: hlankes@gogstats.org.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Lankes
authors.affiliation: Gynecologic Oncology Division, University of Iowa, Gyn/Onc Division, Iowa City, IA 52242, United States. Electronic address: henry-reyes@uiowa.edu.
authors.forename: Henry D
authors.initials: HD
authors.lastname: Reyes
authors.affiliation: Division of Gynecologic Oncology, Maine Medical Center, Scarborough, ME 04101, United States. Electronic address: cdarus@gmail.com.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Darus
authors.affiliation: University of Kansas School of Medicine, Wichita CCOP, Wichita, KS 67208, United States. Electronic address: james.delmore@awhobgyn.com.
authors.forename: James E
authors.initials: JE
authors.lastname: Delmore
authors.affiliation: Division of Gynecologic Oncology, Rush-Presbyterian St. Lukes Medical Center, Chicago, IL 60612, United States. Electronic address: jacob_rotmensch@rush.edu.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rotmensch
authors.affiliation: Dept. of OB/GYN, University of Washington, Seattle, WA 98195, United States. Electronic address: hgray@u.washington.edu.
authors.forename: Heidi J
authors.initials: HJ
authors.lastname: Gray
authors.affiliation: Dept. of OB/GYN, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, United States. Electronic address: robert-mannel@ouhsc.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Mannel
authors.affiliation: Dept. of Gyn/Onc, Indiana University Medical Center, Indianapolis, IN 46202, United States. Electronic address: jschilde@iupui.edu.
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Schilder
authors.affiliation: Ellis Fischel Cancer Center, Columbia, MO 65203, United States. Electronic address: hunterm@health.missouri.edu.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Hunter
authors.affiliation: Dept. of Oncology, Women & Infants Hospital, Providence, RI 02905, United States. Electronic address: McCourtc@wudosis.wustl.edu.
authors.forename: Carolyn K
authors.initials: CK
authors.lastname: McCourt
authors.affiliation: Gynecologic Oncology Division, University of Iowa, Gyn/Onc Division, Iowa City, IA 52242, United States.
authors.forename: Megan I
authors.initials: MI
authors.lastname: Samuelson
authors.affiliation: Gynecologic Oncology Division, University of Iowa, Gyn/Onc Division, Iowa City, IA 52242, United States. Electronic address: Kimberly-leslie@uiowa.edu.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D007211:Indoles
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C500926:cediranib; D007211:Indoles
keywords: Angiogenesis; Fibroblast growth factor receptor; Platelet derived growth factor receptor; Targeted therapy; Tyrosine kinase inhibitor; Vascular endothelial growth factor receptor