Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway Inhibitors

Abstract

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.

Hipertensión arterial y tratamiento del cáncer

“…De modo que si bien los lineamientos generales que establecen las mencionadas guías sobre diagnóstico y tratamiento tienen plena vigencia en los pacientes con cáncer, en aspectos más específicos del manejo debemos basarnos en opiniones de expertos. En el año 2010 se publicó un consenso auspiciado por el Instituto Nacional del Cáncer de Estados Unidos sobre el manejo de la PA entre los pacientes que reciben agentes IA, que fueron reafirmados en un segundo documento en 2012 (22,30) . En 2016, la Sociedad Europea de Cardiología emitió un documento sobre toxicidad cardiovascular durante el tratamiento del cáncer que dedica un capítulo al manejo de la HTA (21) .…”

“…El verapamil y el diltiazem inhiben la vía del citocromo P450 (CYP3A4) e interfieren por este mecanismo con el metabolismo hepático de sunitinib, sorafenib y otras drogas similares, por lo que no deberían utilizarse en conjunto (27,30) .…”

“…Cuando apremia un rápido comienzo de efecto y breve período de titulación de la dosis, un IECA suele ofrecer la respuesta más adecuada como tratamiento inicial (27,30) .…”

“…Usualmente se recomienda no administrar bevacizumab si la presión sistólica es mayor de 160 mmHg o la diastólica mayor de 100 mmHg, o frente a cualquier nivel de hipertensión sintomática al momento del tratamiento. Una vez controlada la situación con el tratamiento antihipertensivo durante el período de suspensión transitoria (usualmente cuatro semanas), la droga puede volver a ser administrada (12,30) .…”

Overview and Management of Cardiac Adverse Events Associated With Tyrosine Kinase Inhibitors

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