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Abstract
Highlights
►
Motesanib is a small molecule inhibitor of multiple receptor tyrosine
kinases including VEGFR 1–3, c-KIT and PDGFR.
► High incidence (4/23) of posterior reversible encephalopathy syndrome with no clear understanding of underlying etiology
► The trial was closed early so no conclusions can be drawn regarding its activity in patients with recurrent ovarian cancer.
► High incidence (4/23) of posterior reversible encephalopathy syndrome with no clear understanding of underlying etiology
► The trial was closed early so no conclusions can be drawn regarding its activity in patients with recurrent ovarian cancer.
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 (posterior) 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.
Highlights
►
Motesanib is a small molecule inhibitor of multiple receptor tyrosine
kinases including VEGFR 1–3, c-KIT and PDGFR.
► High incidence (4/23) of posterior reversible encephalopathy syndrome with no clear understanding of underlying etiology
► The trial was closed early so no conclusions can be drawn regarding its activity in patients with recurrent ovarian cancer.
► High incidence (4/23) of posterior reversible encephalopathy syndrome with no clear understanding of underlying etiology
► The trial was closed early so no conclusions can be drawn regarding its activity in patients with recurrent ovarian cancer.
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