Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors

Dobbin, S. J.H. , Cameron, A. C., Petrie, M. C. , Jones, R. J. , Touyz, R. M. and Lang, N. N. (2018) Toxicity of cancer therapy: what the cardiologist needs to know about angiogenesis inhibitors. Heart, 104(24), pp. 1995-2002. (doi: 10.1136/heartjnl-2018-313726) (PMID:30228246) (PMCID:PMC6268130)

171963.pdf - Accepted Version



Clinical outcomes for patients with a wide range of malignancies have improved substantially over the last two decades. Tyrosine kinase inhibitors (TKIs) are potent signalling cascade inhibitors and have been responsible for significant advances in cancer therapy. By inhibiting vascular endothelial growth factor receptor (VEGFR)-mediated tumour blood vessel growth, VEGFR-TKIs have become a mainstay of treatment for a number of solid malignancies. However, the incidence of VEGFR-TKI-associated cardiovascular toxicity is substantial and previously under-recognised. Almost all patients have an acute rise in blood pressure, and the majority develop hypertension. They are associated with the development of left ventricular systolic dysfunction (LVSD), heart failure and myocardial ischaemia and can have effects on myocardial repolarisation. Attention should be given to rigorous baseline assessment of patients prior to commencing VEGFR-TKIs, with careful consideration of baseline cardiovascular risk factors. Baseline blood pressure measurement, ECG and cardiac imaging should be performed routinely. Hypertension management currently follows national guidelines, but there may be a future role forendothelin-1 antagonism in the prevention or treatment of VEGFR-TKI-associated hypertension. VEGFR-TKI-associated LVSD appears to be independent of dose and is reversible. Patients who develop LVSD and heart failure should be managed with conventional heart failure therapies, but the role of prophylactic therapy is yet to be defined. Serial monitoring of left ventricular function and QT interval require better standardisation and coordinated care. Management of these complex patients requires collaborative, cardio-oncology care to allow the true therapeutic potential from cancer treatment while minimising competing cardiovascular effects.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cameron, Dr Alan and Petrie, Professor Mark and Jones, Professor Robert and Dobbin, Dr Stephen and Touyz, Professor Rhian and Lang, Professor Ninian
Authors: Dobbin, S. J.H., Cameron, A. C., Petrie, M. C., Jones, R. J., Touyz, R. M., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Heart
Publisher:BMJ Publishing Group
ISSN (Online):1468-201X
Published Online:18 September 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Heart 104(24): 1995-2002
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
607381Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762RI CARDIOVASCULAR & MEDICAL SCIENCES