Clinical Toxicity of 4′-Epi-Doxorubicin (Epirubicin)

Epirubicin is a new derivative of doxorubicin characterized by an improved spectrum of activity and a better therapeutic index. At equimolar doses and in comparative studies, epirubicin proved to induce less acute toxicity than doxorubicin, in particular less vomiting, hair loss and myelotoxicity. While giving a comparable response rate in randomized breast cancer studies, epirubicin also proved to be less cardiotoxic than doxorubicin. The reduced potential for cardiac toxicity of epirubicin versus doxorubicin has been shown both by functional assessment (radionuclide cinecardioangiography) and by histopathologic evaluation (endomyocardial biopsies) at equally myelosuppressive doses or at equal doses (equimolar). The lessened cardiotoxicity of epirubicin versus doxorubicin can be explained by the different pharmacokinetic and metabolic properties of these two agents: epirubicin has been found to have a more rapid pharmacokinetic plasma clearance and an additional metabolic pathway (unique glucuronidation).