Author + information
- Alan C. Cameron, MBChB, PhDa,
- Kelly McMahon, BScb,
- Mark Hall, MBChBa,
- Karla B. Neves, PhDa,
- Francisco J. Rios, PhDa,
- Augusto C. Montezano, PhDa,
- Paul Welsh, PhDa,
- Ashita Waterston, MBChB, PhDc,
- Jeff White, MBChB, DMc,
- Patrick B. Mark, MBChB, PhDa,
- Rhian M. Touyz, MBBCh, PhDa and
- Ninian N. Lang, MBChB, PhDa,∗ (, )@ninianlang
- aBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
- bMcGill University Health Centre, McGill University, Montreal, Quebec, Canada
- cDepartment of Medical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
- ↵∗Address for correspondence:
Dr. Ninian N. Lang, BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, 126 University Place, Glasgow G12 8TA, United Kingdom.
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)
This work was supported by the British Heart Foundationhttps://doi.org/10.13039/501100000274 (BHF) [RE/13/5/30177 to Dr. Touyz, BHF Chair CH/12/429762] and the Mason Medical Research Trust. Funding organizations were not involved in the study design or conduct; data collection, analysis and interpretation; nor the preparation, review, or approval of the manuscript. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: CardioOncology author instructions page.
- Received January 15, 2020.
- Revision received June 2, 2020.
- Accepted June 4, 2020.
- 2020 The Authors