title: A phase II evaluation of motesanib (AMG 706) in the treatment of persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas: a Gynecologic Oncology Group study.
abstract: OBJECTIVE
  Vascular endothelial growth factors (VEGF) and their receptors have a critical role in stimulating the growth of ovarian cancer cells. Motesanib is a small molecule inhibitor of multiple receptor tyrosine kinases including VEGF receptors 1-3, as well as c-KIT and platelet-derived growth factor which are related to the VEGF family.
  
  
  METHODS
  Twenty-two eligible patients with recurrent ovarian, fallopian tube or primary peritoneal carcinoma were treated with an oral daily dose of 125 mg of motesanib. Peripheral blood was analyzed for circulating tumor cells (CTC) and circulating endothelial cells/circulating endothelial progenitors (CEC/CEP), VEGF levels and cell-free circulating DNA (cfDNA).
  
  
  RESULTS
  The study was abruptly halted after four patients developed posterior reversible encephalopathy syndrome. One patient had a partial response and seven patients had stable disease at the time they were removed from study treatment. Twelve of the 22 patients (50%) had indeterminate responses at trial closure. Early closure without clinical efficacy data precludes meaningful correlative studies.
  
  
  CONCLUSIONS
  The serious central nervous system toxicity observed in patients with recurrent ovarian cancer precluded full examination of this agent in this population. There were no clear cut explanations for the high incidence of this known class effect in the study population compared with patients with other cancers.
authors: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. russell.schilder@jefferson.edu
authors: R J
authors: RJ
authors: Schilder
authors: M W
authors: MW
authors: Sill
authors: H A
authors: HA
authors: Lankes
authors: M A
authors: MA
authors: Gold
authors: R S
authors: RS
authors: Mannel
authors: S C
authors: SC
authors: Modesitt
authors: P
authors: P
authors: Hanjani
authors: A J
authors: AJ
authors: Bonebrake
authors: A K
authors: AK
authors: Sood
authors: A K
authors: AK
authors: Godwin
authors: W
authors: W
authors: Hu
authors: R K
authors: RK
authors: Alpaugh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000032:analysis; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009841:Oligonucleotides; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D004273:DNA, Neoplasm; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007211:Indoles; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D011505:Protein-Tyrosine Kinases; C519562:imetelstat