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Underestimating Cardiac Toxicity in Cancer Trials:Lessons Learned?
Sunitinib (Sutent; Pfizer, New York, NY) represents one of the
most successful cancer therapies, with US Food and Drug Administration (FDA) approval for three malignancies and ongoing trials in more than 30 tumor types.1,2 It also represents an instructive example revealing how adverse events can be vastly underestimated. The purpose of this article is to critically evaluate the history of the underrecognition of the cardiac toxicity of sunitinib and to propose solutions to improve adverse event monitoring for future therapies.......
"Cardiac toxicity from a wide variety of tyrosine kinase inhibitors
is now recognized to be of importance, with toxicity observed
from both on- and off-target effects. In the case of sunitinib, which
inhibits more than 50 kinases, mechanisms likely include inhibition
of angiogenesis and disturbances of mitochondrial structure
and energy metabolism—both potentially similarly important for
tumor proliferation.11,13"
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