Treating TKI-induced Hypertension in Renal Cell Carcinoma
Inhibiting the VEGF signaling pathway can cause hypertension; there are, however, limited data on managing kinase inhibitor-induced hypertension.
The American Cancer Society estimates that 62,700 new cases of kidney cancer will be diagnosed in the United States in 2016.1 Those with advanced disease may be treated with tyrosine kinase inhibitors (TKIs) that block vascular endothelial growth factor receptors (VEGFR); these agents include sorafenib, sunitinib, pazopanib, cabozantinib, axitinib, and lenvatinib. Although not a kinase inhibitor, bevacizumab also inhibits angiogenesis, and may be used in this treatment setting.
Inhibiting the VEGF signaling pathway can cause hypertension in patients treated with these agents. Although this adverse event is widely observed, there are limited data on managing kinase inhibitor-induced hypertension.2
In 2010, the Investigational Drug Steering Committee of the National Cancer Institute formed an interdisciplinary cardiovascular toxicities expert panel to make recommendations to the Cancer Therapy Evaluation Program on further study of this problem, and to formulate an approach for the management of TKI-induced hypertension by clinicians.
A key recommendation was that the target of blood pressure management should match the Seventh Joint National Committee (JNC 7) guidelines, with a goal blood pressure below 140/90 mmHg for patients without diabetes mellitus or kidney disease, and below 130/80 mmHg for patients with only 1 of these comorbidities.3
JNC 8 updates the committee's recommendations for the management of hypertension. For patients aged 60 years or older, antihypertensive drugs should be initiated when a patient's systolic blood pressure is 150 mmHg or greater, or when diastolic blood pressure is 90 mmHg or greater.4,5