Hypertension in cancer patients treated with anti-angiogenic based regimens.

Yishay Wasserstrum,Oren Pasvolsky,Pia Raanani,Ran Kornowski,Avi Leader,Zaza Iakobishvili

doi:10.1186/s40959-015-0009-4

Abstract

New anti-cancer drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are highly effective in the treatment of solid tumors, however concerns remain regarding their cardiovascular safety. The most common side effect of VEGF signaling pathway (VSP) inhibition is the development of systemic hypertension. We review the incidence, possible mechanisms, significance and management of hypertension in patients treated with VSP inhibitors.

Highlights

The importance of adequate diagnosis and management of hypertension in patients with underlying malignancy is well-known [1]
Pathogenesis of hypertension secondary to VEGF signaling pathway (VSP) inhibition Cancer cell growth and proliferation mostly depends on a blood supply, which is provided through angiogenesis [2]
Other notable VSP inhibitors We found reports of treatment-induced hypertension caused by other TKIs, regarding cabozantinib [88, 89], nintedanib [90, 91] and ponatinib [92], inhibitors of the VEGF and its receptors (VEGFR) pathway

Summary

Background

The importance of adequate diagnosis and management of hypertension in patients with underlying malignancy is well-known [1]. Depending on the type and dose of treatment, systemic hypertension of new-onset is a common side effect of many anticancer agents, the vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. Recent observational study elegantly demonstrates that large artery properties are affected by VSP inhibition by sunitinib or sorafenib These drugs cause the increase in arterial stiffness and this increase is partially independent of the blood pressure change [19]. On-target refers to exaggerated and adverse pharmacologic effects of VSP inhibitors at the target of interest (i.e. VEGF pathway) This concept is further supported by evidence that bevacizumab, a monoclonal anti-VEGF-A antibody, and aflibercept, a soluble receptor with affinity to VEGF-A and -B, are strong inducers of hypertension [20, 21]. Sunitinib Sunitinib malate (Sutent®, SU11248, Pfizer) is multitargeted tyrosine kinase inhibitor (TKI) with inhibitory effects on multiple tyrosine kinase receptors, including VEGFR 1, 2, and 3, platelet-derived growth factor receptors (PDGFR) a and b, FMS

Diastolic Systolic Diastolic Systolic Diastolic

High grade hypertension

Findings

Conclusions