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 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...

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Published in:Gynecologic oncology 2013-04, Vol.129 (1), p.86-91
Main Authors: 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
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Angiogenesis Inhibitors - therapeutic use
Antiangiogenesis
Cancer
DNA, Neoplasm - analysis
Encephalopathy
Fallopian Tube Neoplasms - drug therapy
Female
Glial Cell Line-Derived Neurotrophic Factor - physiology
Hematology, Oncology and Palliative Medicine
Humans
Indoles - adverse effects
Indoles - therapeutic use
Middle Aged
Motesanib
Neoplasm Recurrence, Local - drug therapy
Niacinamide - adverse effects
Niacinamide - analogs & derivatives
Niacinamide - therapeutic use
Obstetrics and Gynecology
Oligonucleotides
Ovarian
Ovarian Neoplasms - drug therapy
Peritoneal Neoplasms - drug therapy
Protein Kinase Inhibitors - therapeutic use
Protein-Tyrosine Kinases - antagonists & inhibitors
Vascular Endothelial Growth Factor A - blood
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Summary:Abstract 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.
ISSN:0090-8258
1095-6859
DOI:10.1016/j.ygyno.2013.01.006