Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics: What Is the Evidence?

Janine A M Kamphuis; Marijke Linschoten; Maarten J Cramer; Eelke H Gort; Anna van Rhenen; Folkert W Asselbergs; Pieter A Doevendans; Arco J Teske

doi:10.1016/j.jaccao.2019.09.007

Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics: What Is the Evidence?

JACC CardioOncol. 2019 Dec 17;1(2):280-290. doi: 10.1016/j.jaccao.2019.09.007. eCollection 2019 Dec.

Authors

Janine A M Kamphuis¹, Marijke Linschoten¹, Maarten J Cramer¹, Eelke H Gort², Anna van Rhenen³, Folkert W Asselbergs^{1

4

5}, Pieter A Doevendans^{1

6}, Arco J Teske¹

Affiliations

¹ Department of Cardiology, Division of Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
² Department of Medical Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
³ Department of Haematology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
⁴ Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, United Kingdom.
⁵ Health Data Research UK and Institute of Health Informatics, University College London, London, United Kingdom.
⁶ Netherlands Heart Institute, Utrecht, the Netherlands.

Abstract

Cancer therapy-related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m²/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted.

Keywords: CTRCD, cancer therapy–related cardiac dysfunction; FDA, Food and Drug Administration; HF, heart failure; MMC, mitomycin C; alkylating therapy; cardiomyopathy; heart failure; risk prediction.

Publication types

Review