St. Francis Hospital and Medical Center, Department of Hematology-Oncology, Medical Oncology and Blood Disorders, LLP, Gothic Park, 43 Woodland Street, Suite G-80, Hartford, CT 06105, USA.
Expert Opin Drug Saf. 2012 May;11(3):445-57. doi: 10.1517/14740338.2012.672971. Epub 2012 Apr 2.
Tyrosine kinase inhibitors (TKIs) have changed the concepts of systemic therapy for a variety of advanced solid and hematologic malignancies. However, their toxicity can be significant, and includes both cardiac and non-cardiac effects.
The authors evaluate comprehensively the adverse cardiovascular portfolio of small molecule TKIs, postulate their underlying mechanisms and offer recommendations regarding prevention and therapy of these toxicities.
For most pan-selective TKIs, there might not be a clear-cut relationship between specific patterns of TK inhibition and cardiovascular toxicity. Cardiovascular side effects are likely due to dysregulation of multiple kinase regulated pathways. The cardiovascular effects of small molecule TKIs include peripheral edema and congestive heart failure, systemic and pulmonary hypertension, acute coronary syndromes and cardiac arrest due to QTc prolongation. Caution should be sought in patients with pre-existing cardiac dysfunction before initiating any of these agents. It is hoped that newer TKI generations will display minimal if any cardiovascular toxicity, while maintaining their anticancer efficacy. As of today, the high likelihood of morbidity without treatment mandates that cardiovascular toxicity of TKIs be carefully assessed and balanced with the known benefits of administering these agents.
酪氨酸激酶抑制剂（TKIs）改变了多种晚期实体瘤和血液系统恶性肿瘤的全身治疗观念。然而，其毒性可能很显著，包括心脏毒性和非心脏毒性。
作者全面评估了小分子 TKI 的不良心血管风险，推测其潜在机制，并就这些毒性的预防和治疗提出建议。
对于大多数泛选择性 TKI，特定的 TKI 抑制模式与心血管毒性之间可能没有明确的关系。心血管副作用可能是由于多个受激酶调节的途径失调所致。小分子 TKI 的心血管作用包括外周水肿和充血性心力衰竭、全身和肺动脉高压、急性冠状动脉综合征和因 QTc 延长导致的心脏骤停。在开始使用这些药物之前，应谨慎评估有预先存在的心脏功能障碍的患者。希望新一代 TKI 在保持抗癌疗效的同时，显示出最小的（如果有的话）心血管毒性。截至目前，如果不进行治疗，这些药物的发病率极高，因此必须仔细评估 TKI 的心血管毒性，并权衡使用这些药物的已知益处。
