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J Cardiovasc Pharmacol Ther ; 23(5): 387-398, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29706106

RESUMO

Pazopanib is an approved treatment for renal cell carcinoma and a second-line treatment for nonadipocytic soft-tissue sarcoma. However, its clinical efficacy is limited by its cardiovascular side effects. Pazopanib and other vascular endothelial growth factor receptor tyrosine kinase inhibitors have been associated with the development of hypertension, QT interval prolongation, and other cardiovascular events; however, these mechanisms are largely unknown. Gaining a deeper understanding of these mechanisms is essential for the development of appropriate surveillance strategies and possible diagnostic biomarkers to allow us to monitor patients and modulate therapy prior to significant cardiac insult. This approach will be vital in keeping patients on these life-saving therapies and may be applicable to other tyrosine kinase inhibitors as well. In this review, we provide a comprehensive overview of the preclinical and clinical side effects of pazopanib with a focus on the mechanisms responsible for its toxicity to the cardiovascular system.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Sistema Cardiovascular/efeitos dos fármacos , Neoplasias Renais/tratamento farmacológico , Pirimidinas/efeitos adversos , Sarcoma/tratamento farmacológico , Neoplasias de Tecidos Moles/tratamento farmacológico , Sulfonamidas/efeitos adversos , Inibidores da Angiogênese/farmacocinética , Animais , Carcinoma de Células Renais/patologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/fisiopatologia , Humanos , Indazóis , Neoplasias Renais/patologia , Pirimidinas/farmacocinética , Medição de Risco , Fatores de Risco , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Sulfonamidas/farmacocinética , Resultado do Tratamento
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