Anthracycline-induced cardiotoxicity: course, pathophysiology, prevention and management

Abstract

Although effective anti-neoplastic agents, anthracyclines are limited by their well recognized and pervasive cardiotoxic effects. The incidence of late progressive cardiovascular disease in long-term survivors of cancer is established and may contribute to heart failure and death. To maximize the benefits of these drugs, a high-risk population has been identified and new strategies have been investigated to minimize toxic effects, including limiting the cumulative dose, controlling the rate of administration and using liposomal preparations and novel anthracycline analogues. Dexrazoxane also shows promise as a cardioprotectant during treatment. This paper reviews these strategies, as well as medications used to manage anthracycline-induced cardiotoxicity, and functional and biochemical means of monitoring cardiotoxicity, including echocardiography, radionuclide scans and biomarker analysis. The treatment of adult cancer survivors who have had anthracycline-related cardiotoxicity has not been systematically studied. Empirically, anthracycline-associated cardiac dysfunction is treated very similarly to other forms of heart failure. These treatments include avoiding additional cardiotoxic regimens, controlling hypertension, lifestyle changes, medications and heart transplantation.

Keywords::

• ACE inhibitors
• anthracyclines
• β-blockers
• cardiotoxicity
• dexrazoxane
• doxorubicin
• epirubicin
• heart failure
• idarubicin
• liposomal doxorubicin
• mitoxantrone

Disclosure

Dr Lipshultz’s research is supported, in part, by the National Cancer Institute, the National Heart, Lung and Blood Institute, the Lance Armstrong Foundation, the Women’s Cancer Association, the Children’s Cardiomyopathy Foundation, Novartis, Roche Diagnostics and Pfizer Pharmaceuticals.

This paper has been supported in part by grants from the National Cancer Institute (CA68484-SL, CA34183-SL, CA79060-SL, CA06516-SL), National Heart, Lung, and Blood Institute (HL69800-SL, HL53392-SL, HL59837-SL, HL53392-SL), the Lance Armstrong Foundation (SE Lipshultz, TL Miller and E Barry), the Children’s Cardiomyopathy Foundation (SE Lipshultz and TL Miller) and the Leukemia and Lymphoma Society (E Barry). In addition, T Lang, MA of Tom Lang Communications and Training has been compensated for the pre-submission editorial review of the manuscript.