抗血管内皮生长因子治疗与心血管毒性：哪些是需要靶向的重要临床标志物？
Anti-vascular endothelial growth factor therapies and cardiovascular toxicity: what are the important clinical markers to target?
机构信息
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
出版信息
Oncologist. 2010;15(2):130-41. doi: 10.1634/theoncologist.2009-0252. Epub 2010 Feb 5.
BACKGROUND
Therapies targeting vascular endothelial growth factor (VEGF) are associated with hypertension, cardiotoxicity, and thromboembolic events.
METHODS
All prospective phase I-III clinical trials published up to December 2008 of approved anti-VEGF therapies (bevacizumab, sunitinib, sorafenib) and relevant literature were reviewed.
RESULTS
The rates of Common Toxicity Criteria (version 3) grade 3-4 hypertension with bevacizumab, sunitinib, and sorafenib were 9.2%, 6.9%, and 7.2%, respectively. Grade 3-4 left ventricular systolic dysfunction was noted in 0.3%, 1.4%, and 0.05% of patients, respectively, whereas the rates of grade 3-4 thromboembolism were 9.6%, 1.2%, and 3.8%, respectively. The renin-angiotensin-aldosterone system (RAAS) may play a key role in vasoconstriction and capillary rarefaction, which are unleashed when VEGF signaling is targeted. Inhibiting RAAS may be the optimal approach for managing these toxicities.
CONCLUSIONS
In anticipation of cardiovascular complications with anti-VEGF therapies, early detection and personalized management may improve clinical outcomes and tolerance.
背景
针对血管内皮生长因子（VEGF）的治疗与高血压、心脏毒性和血栓栓塞事件有关。
方法
回顾了截至 2008 年 12 月批准的抗 VEGF 治疗药物（贝伐单抗、舒尼替尼、索拉非尼）的所有前瞻性 I-III 期临床试验和相关文献。
结果
贝伐单抗、舒尼替尼和索拉非尼治疗的常见毒性标准（第 3 版）3-4 级高血压发生率分别为 9.2%、6.9%和 7.2%。分别有 0.3%、1.4%和 0.05%的患者出现 3-4 级左心室收缩功能障碍，而 3-4 级血栓栓塞的发生率分别为 9.6%、1.2%和 3.8%。肾素-血管紧张素-醛固酮系统（RAAS）可能在血管收缩和毛细血管稀疏中发挥关键作用，而血管内皮生长因子信号靶向治疗时会释放这种作用。抑制 RAAS 可能是管理这些毒性的最佳方法。
结论
为预防抗 VEGF 治疗的心血管并发症，早期检测和个体化管理可能会改善临床结果和耐受性。
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