Vascular Toxicities of Cancer Therapies

Abstract

Since the late 1990s, there has been a steady decline in cancer-related mortality, in part related to the introduction of so-called “targeted therapies”. Intended to interfere with a specific molecular pathway, these therapies have, paradoxically, led to a number of “off-target” effects. The latest examples are tyrosine kinase inhibitors targeting the Philadelphia Chromosome mutation product, which have been associated with progressive atherosclerosis and acute vascular events. Additionally, agents designed to interfere with the vascular growth factor signaling pathway have vascular side effects ranging from hypertension to arterial events and cardiomyocyte toxicity. Interestingly, the risk of cardiotoxicity with drugs such as trastuzumab is predicted by preexisting cardiovascular risk factors and disease, posing the question of a vascular component to the pathophysiology. The effect on the coronary circulation has been the leading explanation for cardiotoxicity of 5-Fluorouracil and may be the underlying the mechanism of presentation of apical ballooning syndrome with various chemotherapeutics. Classical chemotherapeutics such as cisplatin, often used in combination with bleomycin and vinca alkaloids, can lead to vascular events including acute coronary thrombosis, may be associated with an increased long-term cardiovascular risk. This review is intended to provide an update on the evolving spectrum of vascular toxicities with cancer therapeutics, particularly as it pertains to clinical practice as well as the conceptualization of cardiovascular diseases. Vascular toxicity with cancer therapy: the old and the new, an evolving avenue.

Lower cutaneous microvascular reactivity in adult cancer patients receiving chemotherapy

“…We chose noninvasive iontophoresis drug delivery over intradermal microdialysis to eliminate both the needle trauma and pain associated with intradermal microdialysis. This is critical given the limited understanding of the vascular consequences of chemotherapy (34,48) and the fact that placement of intradermal microdialysis fibers has the potential to alter vasodilator responses (35). Briefly, an iontophoresis drug delivery probe with an integrated laser Doppler probe and temperature regulator was placed on the left forearm 15 cm away from a conductive hydrogel drug-dispersive electrode (PF 384; Perimed, Järfälla, Sweden).…”

“…Many cancers, like breast cancer and lymphoma, are currently treated with a variety of chemotherapy agents that are associated with cardiotoxic syndromes, with the development of left ventricular dysfunction being the most prevalent (70). However, other clinical manifestations of cardiotoxicity, particularly those associated with vascular dysfunction, have also been reported (34,60), suggesting that asymptomatic changes in vascular function may be occurring during cancer treatment. In animal models, doxorubicin chemotherapy has been shown to significantly impair endothelium-dependent vasodilation to acetylcholine (ACh) (21,29).…”

May a sigma‐1 antagonist improve neuropathic signs induced by cisplatin and vincristine in rats?

“…In addition, chemotherapy also induces gastrointestinal impairment (Schwartzberg, 2007), and cardiovascular toxicity (Herrmann et al, 2016). We included the evaluation of MR-309's effect on the signs of nausea from chronic administration of CIS, the most emetogenic antitumoural drug available (Cabezos et al, 2008).…”

Comprehensive review on cardio-oncology: Role of multimodality imaging

“…In addition, CV risk is escalated by the type of chemotherapy agent, particularly with targeted therapies, such as tyrosine kinase inhibitors, which inhibit several cardiomyocyte signaling pathways, including the vascular endothelial growth factor (VEGF) signaling pathway, which seems to play an essential role in maintaining normal endothelial control of vasomotor tone. 116 As outlined by the Society for Cardiovascular Angiography and Interventions (SCAI), 47 right and left heart catheterizations are reasonable for preoperative planning for patients with radiation-induced heart disease (RIHD) and evaluation of pericardial constriction and restrictive cardiomyopathy, when noninvasive imaging is nondiagnostic. Right heart catheterization is indicated for the evaluation of HF, assessment of constrictive or restrictive cardiomyopathy, pulmonary hypertension, pericardial disease, and valvular disease.…”

“…Common chemotherapy agents associated with cardiovascular toxicity25,30,31,47,116 Left ventricular dysfunction, heart failure, HTN, Angina, MI, Takotsubo cardiomyopathy, Raynaud's stroke, DVT/PE effusion and constriction, and valvular damage (…”