Division of Cardiology and Feinberg Cardiovascular Research Institute, Northwestern University, 303 East Chicago Avenue, Chicago, IL 60611, USA.
Curr Hypertens Rep. 2011 Dec;13(6):430-5. doi: 10.1007/s11906-011-0229-4.
Kinase inhibitors have emerged as an important new class of agents for the treatment of diverse tumors. Sunitinib malate is a small-molecule, oral, multi-kinase inhibitor approved for use in treating renal cell carcinoma and gastrointestinal stromal tumor. It has also demonstrated efficacy in treating pancreatic neuroendocrine tumors and is being evaluated for the treatment of other cancers. Initially developed for its inhibition of the vascular endothelial growth factor (VEGF) signaling pathway, sunitinib has been associated with hypertension and heart failure. This review examines the incidence and severity of these adverse events, relevant findings from other agents that inhibit VEGF signaling, the mechanisms underlying these effects, and suggestions for their clinical management. Hypertension is a common adverse effect that is usually easily managed. The associated heart failure is less common; it can be reversible but must be actively monitored and managed. Mechanistic insights suggest that an attentive clinical strategy for hypertension could prevent severe cardiotoxicity.
激酶抑制剂已成为治疗多种肿瘤的一类重要新药。苹果酸舒尼替尼是一种小分子、口服、多激酶抑制剂，已被批准用于治疗肾细胞癌和胃肠道间质瘤。它在治疗胰腺神经内分泌肿瘤方面也显示出疗效，目前正在评估用于治疗其他癌症。舒尼替尼最初是为了抑制血管内皮生长因子 (VEGF) 信号通路而开发的，它与高血压和心力衰竭有关。本综述检查了这些不良事件的发生率和严重程度、其他抑制 VEGF 信号的药物的相关发现、这些影响的潜在机制，以及对其临床管理的建议。高血压是一种常见的不良反应，通常很容易控制。相关的心力衰竭则较为少见；它可能是可逆的，但必须进行积极监测和管理。机制研究表明，高血压的精心临床策略可能预防严重的心脏毒性。
