Justice Cody N, Derbala Mohamed H, Baich Tesla M, Kempton Amber N, Guo Aaron S, Ho Thai H, Smith Sakima A
1 Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, USA.
2 Mayo Clinic Scottsdale, Arizona, Phoenix, AZ, USA.
J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):387-398. doi: 10.1177/1074248418769612. Epub 2018 Apr 29.
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.
帕唑帕尼是一种已获批准用于治疗肾细胞癌的药物,也是非脂肪细胞性软组织肉瘤的二线治疗药物。然而,其临床疗效受到心血管副作用的限制。帕唑帕尼和其他血管内皮生长因子受体酪氨酸激酶抑制剂与高血压、QT间期延长及其他心血管事件的发生有关;然而,这些机制在很大程度上尚不清楚。深入了解这些机制对于制定适当的监测策略和可能的诊断生物标志物至关重要,以便我们在患者发生严重心脏损伤之前对其进行监测并调整治疗方案。这种方法对于让患者持续接受这些挽救生命的治疗至关重要,并且可能也适用于其他酪氨酸激酶抑制剂。在本综述中,我们全面概述了帕唑帕尼的临床前和临床副作用,重点关注其对心血管系统产生毒性的机制。