title: A phase II evaluation of pazopanib in the treatment of recurrent or persistent carcinosarcoma of the uterus: a gynecologic oncology group study.
abstract: OBJECTIVE
  Carcinosarcomas of the female genital tract, also called malignant mixed müllerian tumors, are aggressive biphasic tumors. Second-line treatment options in the recurrent/persistent setting have yielded marginal responses. Given the potential role of angiogenesis in the gynecological carcinomas, pazopanib, a VEGFR inhibitor, was investigated in the management of patients with recurrent carcinosarcoma of the uterus.
  
  
  METHODS
  Eligible patients had histologically confirmed carcinosarcoma of the uterus, a maximum of two prior lines of therapy, adequate renal, hepatic and hematologic function and a performance status of 0-2. Pazopanib was administered orally at 800mg. Two dose reductions were allowed. The primary objective was to ascertain the activity of pazopanib as measured by the proportion of patients who survive progression-free for at least six months and the proportion of patients that have objective tumor responses. Secondary objectives included the frequency and severity of adverse events as assessed by CTCAE v4.0.
  
  
  RESULTS
  Of the 22 enrolled patients, 19 were eligible and evaluable for toxicity and survival. No patients had a partial or complete response (90% confidence interval [CI]: 0%, 14.6%). Three patients (15.8%) had PFS ≥6months (90% CI: 4.4%, 35.9%). The median PFS was 2.0months (first and third quartiles were 1.6 and 4.0months, respectively). The median overall survival was 8.7months (first and third quartiles were 2.6 and 14.0months, respectively).
  
  
  CONCLUSIONS
  Pazopanib demonstrated minimal activity as a second or third line treatment for advanced uterine carcinosarcoma. Potential clinical trial participation should be discussed with the patients.
authors.affiliation: Dana-Farber Partners Cancer Care, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Electronic address: Susana_Campos@dfci.harvard.edu.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Campos
authors.affiliation: Gynecologic Oncology Group Statistical & Data Center, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Brady
authors.affiliation: University of Oklahoma Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Moxley
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Roisin E
authors.initials: RE
authors.lastname: O'Cearbhaill
authors.affiliation: Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Paula S
authors.initials: PS
authors.lastname: Lee
authors.affiliation: Women & Infants Hospital, Providence, RI 02905, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: DiSilvestro
authors.affiliation: Rush-Presbyterian St. Lukes Medical Center, Chicago, IL 60612, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Rotmensch
authors.affiliation: Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Rose
authors.affiliation: Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Premal H
authors.initials: PH
authors.lastname: Thaker
authors.affiliation: Ohio State University, Columbus Cancer Council, Hilliard, OH 43026, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: O'Malley
authors.affiliation: Abington Memorial Hospital, Abington, PA 19001, USA.
authors.forename: Parviz
authors.initials: P
authors.lastname: Hanjani
authors.affiliation: University of Oklahoma Science Center, Oklahoma City, OK 73104, USA.
authors.forename: Rosemary E
authors.initials: RE
authors.lastname: Zuna
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Martee L
authors.initials: ML
authors.lastname: Hensley
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D002296:Carcinosarcoma / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011743:Pyrimidines / Q000627:therapeutic use*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Angiogenesis; Carcinosarcoma; Uterus; VEGFR inhibitors