Department of Medicine, University of Chicago Medical Center, 5841Chicago, IL 60637, USA.
J Natl Cancer Inst. 2010 May 5;102(9):596-604. doi: 10.1093/jnci/djq091. Epub 2010 Mar 29.
Hypertension is a mechanism-based toxic effect of drugs that inhibit the vascular endothelial growth factor signaling pathway (VSP). Substantial evidence exists for managing hypertension as a chronic condition, but there are few prospectively collected data on managing acute hypertension caused by VSP inhibitors. The Investigational Drug Steering Committee of the National Cancer Institute convened an interdisciplinary cardiovascular toxicities expert panel to evaluate this problem, to make recommendations to the Cancer Therapy Evaluation Program on further study, and to structure an approach for safe management by treating physicians. The panel reviewed: the published literature on blood pressure (BP), hypertension, and specific VSP inhibitors; abstracts from major meetings; shared experience with the development of VSP inhibitors; and established principles of hypertension care. The panel generated a consensus report including the recommendations on clinical concerns summarized here. To support the greatest possible number of patients to receive VSP inhibitors safely and effectively, the panel had four recommendations: 1) conduct and document a formal risk assessment for potential cardiovascular complications, 2) recognize that preexisting hypertension will be common in cancer patients and should be identified and addressed before initiation of VSP inhibitor therapy, 3) actively monitor BP throughout treatment with more frequent assessments during the first cycle of treatment, and 4) manage BP with a goal of less than 140/90 mmHg for most patients (and to lower, prespecified goals in patients with specific preexisting cardiovascular risk factors). Proper agent selection, dosing, and scheduling of follow-up should enable maintaining VSP inhibition while avoiding the complications associated with excessive or prolonged elevation in BP.
高血压是一种药物抑制血管内皮生长因子信号通路(VSP)的基于机制的毒性效应。有大量证据表明高血压是一种慢性疾病,但对于 VSP 抑制剂引起的急性高血压,仅有少数前瞻性收集的数据。国家癌症研究所的研究药物指导委员会召集了一个跨学科心血管毒性专家小组,以评估这一问题,向癌症治疗评估计划提出进一步研究的建议,并为治疗医生的安全管理制定方法。该小组审查了:关于血压(BP)、高血压和特定 VSP 抑制剂的已发表文献;主要会议的摘要;VSP 抑制剂开发的共享经验;以及高血压护理的既定原则。小组生成了一份共识报告,包括这里总结的临床关注建议。为了支持尽可能多的患者安全有效地接受 VSP 抑制剂,该小组提出了四项建议:1)进行并记录潜在心血管并发症的正式风险评估,2)认识到癌症患者中常见的高血压,应在开始 VSP 抑制剂治疗前识别并解决,3)在治疗期间积极监测血压,在治疗的第一个周期中更频繁地评估,4)以低于 140/90mmHg 为大多数患者的目标管理血压(并在具有特定既往心血管危险因素的患者中降低规定的目标)。适当的药物选择、剂量和随访安排应能够在避免与血压过度或持续升高相关的并发症的同时维持 VSP 抑制。