Acute blood pressure elevation associated with biological therapies for cancer: a focus on VEGF signaling pathway inhibitors

ABSTRACT

Introduction: Treatment with biological agents interfering with mechanisms of angiogenesis, such as vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors, was associated with an enhanced risk of acute and severe blood pressure (BP) increase and development of hypertensive emergencies.

Areas covered: The present article will review the scientific literature reporting hypertensive emergencies as a complication of biological treatment with VSP inhibitors. Hypertensive emergency is a life-threatening condition characterized by very high BP values (>180/110 mmHg) associated with acute organ damage. The exact mechanism of action is still incompletely clarified. Endothelial dysfunction following reduced bioavailability of nitric oxide has been hypothesized to play an important role in promoting hypertension and the occurrence of acute organ damage.

Expert opinion: Prevention, prompt recognition and treatment of hypertensive emergencies associated with treatment with VSP-inhibitors are essential to reduce the risk of adverse events. Not infrequently, the occurrence of hypertensive emergency led to VSP treatment discontinuation, with potential negative consequences on patient overall survival. The present review aims at providing detailed knowledge for the clinician regarding this specific issue, which could be of high impact in usual clinical practice, given the increasing burden of indications to treatment with biological agents targeted to the VEGF pathway.

KEYWORDS:

• Arterial hypertension
• hypertensive emergencies
• cancer therapies
• angiogenesis inhibitors
• anti VEGF drugs
• endothelial cells

Article highlights

• Treatment with biological agents interfering with mechanisms of angiogenesis, such as vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors, is associated with an enhanced risk of hypertensive emergencies.

• The possible link is represented by pharmacological inhibition of nitric oxide (NO) synthesis, impaired endothelium-mediated vasodilation, vasoconstriction, and microvascular damage

• Development of hypertension is the most frequent adverse event recorded in patients treated with VSP-inhibitors. Incidence of severe hypertension with associated organ damage is reported to be about 0.5–1.5%

• BP increases may constitute a life-threatening condition, when associated with acute hypertension-mediated organ damage such as malignant hypertension, acute kidney dysfunction, cardiac and cerebral ischemia, pulmonary edema, hypertensive encephalopathy, and acute aortic disease

• There is a knowledge gap about the prognosis of severe hypertension with associated organ damage induced by VSP-inhibitors. Systematic reporting in case series and clinical trials is mandatory in order to fill this gap in the future

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.