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Schilder RJ , Sill MW , Lankes HA , Gold MA , Mannel RS , Modesitt SC , Hanjani P , Bonebrake AJ , Sood AK , Godwin AK , Hu W , Alpaugh RK
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
Gynecol Oncol. 2013 Apr;129(1) :86-91
PMID: 23321064    PMCID: PMC 3712785   
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OBJECTIVES: 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. PATIENTS AND 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.
Schilder, R J Sill, M W Lankes, H A Gold, M A Mannel, R S Modesitt, S C Hanjani, P Bonebrake, A J Sood, A K Godwin, A K Hu, W Alpaugh, R K CA 27469/CA/NCI NIH HHS/United States CA 37517/CA/NCI NIH HHS/United States CA006927/CA/NCI NIH HHS/United States CA140323/CA/NCI NIH HHS/United States P50 CA083638/CA/NCI NIH HHS/United States P50 CA083639/CA/NCI NIH HHS/United States P50CA83639/CA/NCI NIH HHS/United States Clinical Trial, Phase II Research Support, N.I.H., Extramural United States Gynecologic oncology Gynecol Oncol. 2013 Apr;129(1):86-91. doi: 10.1016/j.ygyno.2013.01.006. Epub 2013 Jan 13.