Comprehensive characterisation of the vascular effects of cisplatin-based chemotherapy in patients with testicular cancer

Cameron, A. C. et al. (2020) Comprehensive characterisation of the vascular effects of cisplatin-based chemotherapy in patients with testicular cancer. JACC: CardioOncology, 2(3), pp. 443-455. (doi: 10.1016/j.jaccao.2020.06.004)

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Abstract

Background: Cisplatin-based chemotherapy increases the risk of cardiovascular and renal disease. Objectives: We aimed to define the time course, pathophysiology, and approaches to prevent cardiovascular disease associated with cisplatin-based chemotherapy. Methods: Two cohorts of patients with a history of testicular cancer (n = 53) were recruited. Cohort 1 consisted of 27 men undergoing treatment with: 1) surveillance; 2) 1 to 2 cycles of bleomycin, etoposide, and cisplatin (BEP) chemotherapy (low-intensity cisplatin); or 3) 3 to 4 cycles of BEP (high-intensity cisplatin). Endothelial function (percentage flow-mediated dilatation) and cardiovascular biomarkers were assessed at 6 visits over 9 months. Cohort 2 consisted of 26 men previously treated 1 to 7 years ago with surveillance or 3 to 4 cycles BEP. Vasomotor and fibrinolytic responses to bradykinin, acetylcholine, and sodium nitroprusside were evaluated using forearm venous occlusion plethysmography. Results: In cohort 1, the percentage flow-mediated dilatation decreased 24 h after the first cisplatin dose in patients managed with 3 to 4 cycles BEP (10.9 ± 0.9 vs. 16.7 ± 1.6; p < 0.01) but was unchanged from baseline thereafter. Six weeks after starting 3 to 4 cycles BEP, there were increased serum cholesterol levels (7.2 ± 0.5 mmol/l vs. 5.5 ± 0.2 mmol/l; p = 0.01), hemoglobin A1c (41.8 ± 2.0 mmol/l vs. 35.5 ± 1.2 mmol/l; p < 0.001), von Willebrand factor antigen (62.4 ± 5.4 mmol/l vs. 45.2 ± 2.8 mmol/l; p = 0.048) and cystatin C (0.91 ± 0.07 mmol/l vs. 0.65 ± 0.09 mmol/l; p < 0.01). In cohort 2, intra-arterial bradykinin, acetylcholine, and sodium nitroprusside caused dose-dependent vasodilation (p < 0.0001). Vasomotor responses, endogenous fibrinolytic factor release, and cardiovascular biomarkers were not different in patients managed with 3 to 4 cycles of BEP versus surveillance. Conclusions: Cisplatin-based chemotherapy induces acute and transient endothelial dysfunction, dyslipidemia, hyperglycemia, and nephrotoxicity in the early phases of treatment. Cardiovascular and renal protective strategies should target the early perichemotherapy period. (Clinical Characterisation of the Vascular Effects of Cis-platinum Based Chemotherapy in Patients With Testicular Cancer [VECTOR], NCT03557177; Intermediate and Long Term Vascular Effects of Cisplatin in Patients With Testicular Cancer [INTELLECT], NCT03557164)

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Rios, Dr Francisco and Hall, Dr Mark and Mark, Dr Patrick and Welsh, Dr Paul and McMahon, Ms Kelly and Lang, Dr Ninian and Cameron, Dr Alan and Montezano, Dr Augusto and White, Dr Jeffery and Touyz, Professor Rhian and Neves, Dr Karla
Authors: Cameron, A. C., McMahon, K., Hall, M., Neves, K. B., Rios, F. J., Montezano, A. C., Welsh, P., Waterston, A., White, J., Mark, P. B., Touyz, R. M., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:JACC: CardioOncology
Publisher:American College of Cardiology
ISSN:2666-0873
ISSN (Online):2666-0873
Published Online:15 September 2020
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in JACC: CardioOncology 2(3):443-455
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science