Doxorubicin or Epirubicin Versus Liposomal Doxorubicin Therapy-Differences in Cardiotoxicity.

Abstract

Doxorubicin (DOX) is an important drug used in the treatment of many malignancies. Unfortunately DOX causes various side effects, with cardiotoxicity being the most characteristic. Risk factors for DOX induced cardiotoxicity (DIC) include cumulative dose of DOX, preexisting cardiovascular diseases, dyslipidemia, diabetes, smoking, along with the use of other cardiotoxic agents. Development of DIC is associated with many pathological phenomena - increased oxidative stress, as well as upregulation of ferroptosis, apoptosis, necrosis, and autophagy. In DIC expression of many microRNAs is also deregulated. In order to avoid cardiotoxicity and still use DOX effectively DOX derivatives such as epirubicin were synthesized. Nowadays a new liposomal form of DOX (L-DOX) appeared as an alternative to conventional treatment with greatly reduced cardiotoxicity. L-DOX can be divided into two groups of substances - pegylated (PLD) with increased solubility and stability, and non-pegylated (NLPD). Many metaanalyses, clinical along with preclinical studies have shown L-DOX treatment is associated with a smaller decrease of left ventricular ejection fraction (LVEF) and other heart functions, but efficacy of this treatment is comparable to the use of convenctional DOX.