Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management

Prog Cardiovasc Dis. Mar-Apr 2007;49(5):330-52. doi: 10.1016/j.pcad.2006.10.002.

Abstract

First isolated in the early 1960s, doxorubicin (DOX) remains among the most effective anticancer drug ever developed. However, this drug has proven to be a double-edged sword because it also causes a cardiomyopathy that leads to a form of congestive heart failure that is usually refractory to common medications. It is hoped that a better understanding of the mechanisms underlying DOX's cardiotoxicity will enable development of therapies with which to prevent and/or treat the heart failure it causes. Suggested contributors to DOX-induced cardiomyopathy include formation of reactive oxygen species, apoptosis, inhibited expression of cardiomyocyte-specific genes, and altered molecular signaling. And taking these various contributors into consideration, a variety of approaches aimed at preventing or mitigating the cardiotoxicity of DOX have been tried, but so far, the ability of these treatments to protect the heart from damage has been limited. That said, one recent approach that shows promise is adjuvant therapy with a combination of hematopoietic cytokines, including erythropoietin, granulocyte colony-stimulating factor, and thrombopoietin. We suggest this approach to preventing DOX-induced cardiomyopathy is worthy of serious consideration for clinical use.

Publication types

  • Review

MeSH terms

  • Antibiotics, Antineoplastic / toxicity*
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / diagnostic imaging
  • Cardiomyopathies / pathology
  • Cardiomyopathies / prevention & control*
  • Doxorubicin / toxicity*
  • Humans
  • Myocardium / pathology*
  • Necrosis / chemically induced
  • Ultrasonography

Substances

  • Antibiotics, Antineoplastic
  • Doxorubicin