Patients with cancer whose treatment includes any drug that inhibits signaling via the vascular endothelial growth factor (VEGF) pathway should receive regular blood pressure (BP) monitoring according to a panel of experts convened by the Angiogenesis Task Force of the National Cancer Institute Investigational Drug Steering Committee. Panel members, all experts in managing cardiovascular toxicities, determined that hypertension is a “mechanism-based toxic effect” of VEGF inhibitors. They outlined a set of 4 principles for managing elevated BP when using VEGF inhibitors to induce angiogenesis, a therapeutic approach the experts acknowledged is effective in patients with cancer (Table 1).
The panel reviewed studies in the literature that examined the relationship between BP, hypertension, and a specified VEGF inhibitor. The group also reviewed abstracts presented at major oncology meetings and assessed available data compiled during the development of these drugs. According to the investigators, “BP elevation is an effect common to all VEGF signaling pathway inhibitors, with hypertension reported as an adverse event in every trial of these drugs,” though they were not certain exactly how these inhibitors elevate BP. The researchers said VEGF inhibitors are also associated with hemorrhage, thrombosis, nephrotoxicity, and cardiac toxic effects, but the scope of their recommendations was limited to the more common and addressable concern of elevated BP.
In patients without cancer, chronic hypertension has been linked to congestive heart failure, myocardial infarction, stroke, and renal compromise, all conditions that increase rates of morbidity and mortality. According to the panel, managing chronic hypertension reduces the 10-year mortality rate by 9%. There are various algorithms and guidelines for long-term management of BP in general, but these may not be applicable to patients with metastatic cancer whose life expectancy is limited.
The researchers noted some might favor “minimalist approaches to hypertension for patients with incurable disease,” but they believe properly managing comorbidities such as hypertension might improve overall survival. In some cases, controlling hypertension might allow the patient to tolerate a higher dose of the VEGF inhibitor, contributing to improved survival outcomes.
Pretreatment Risk Assessment
The panel recommended conducting a “formal risk assessment for potential cardiovascular complications” before treating patients with a VEGF inhibitor. This should include at least 2 BP readings measured at different visits, obtaining a thorough patient history, and conducting a comprehensive examination to assess cardiovascular risk factors. Certain laboratory tests may also be required. Patients who have not been screened recently for cardiovascular disease will require an electrocardiogram and tests to measure serum cholesterol, triglycerides, and fasting plasma glucose before receiving VEGF inhibitors. Any pretreatment risk assessment should factor in subclinical organ damage and comorbidities. The panel suggested clinicians use the European Society of Hypertension/European Society of Cardiology system (Table 2) for assessing cardiovascular risk. Patients with no risk factors are considered low risk, those with 1 factor are high risk, and patients with ≥2 factors are higher risk.
The panel cautioned against dismissing high BP readings as a byproduct of “white coat hypertension” or uncontrolled pain. In cases where patients do have uncontrolled pain, the authors said the baseline measurement should be reassessed once the pain is better controlled. Clinicians should keep in mind that nonsteroidal anti-inflammatory drugs can increase BP, whereas narcotics and sufficient pain control are known to lower BP.
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