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

Abstract

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).

Epirubicin as part of a multi‐agent chemotherapy protocol for canine lymphoma

“…To the authors' knowledge there is no published pharmacokinetic or pharmacodynamic data for dogs receiving epirubicin. A dose of 30 mg/m 2 was chosen based on published human data revealing equal tumour responses and potentially lesser toxicity at epirubicin doses equipotent to doxorubicin ; 30 mg/m 2 is the standard doxorubicin dose used in veterinary medicine CHOP‐based protocols.…”

“…Epirubicin (4‐epidoxorubicin) is a semi‐synthetic stereoisomer of the anthracycline doxorubicin developed in an effort to find agents with at least equal or greater efficacy, but less cardiotoxicity, than doxorubicin. Epirubicin differs from doxorubicin only in the spatial orientation of the hydroxyl group in the 4 ′ carbon position (equatorial instead of axial) of the amino‐sugar moiety. This small positional change does not alter its mode of action or spectrum of activity compared to doxorubicin but causes a number of pharmacokinetic and metabolic changes that lead to enhanced total body clearance and a shorter terminal half life.…”

“… Animal models and human clinical trials revealed the anti‐tumour activity of epirubicin to be equipotent to doxorubicin but there to be reduced toxicity, particularly cardiotoxicity. Given the reduced toxicity and equipotent activity, epirubicin is currently used extensively in the treatment of a range of human malignancies including breast cancer and lymphoma. In contrast, the use of epirubicin has been infrequently described in veterinary medicine.…”

Protecting against anthracycline‐induced myocardial damage: a review of the most promising strategies

“…Idarubicin was more potent and more active than daunorubicin and doxorubicin in several experimental leukaemias (Ganzina et al , 1985; Carella et al , 1990). In preclinical and animal studies, the cardiac toxicity was substantially lower than that of doxorubicin (Anderlini et al , 1995; Platel et al , 1999).…”

Πρόληψη της καρδιοτοξικότητας από ανθρακυκλίνες με β-αποκλειστές και Α-ΜΕΑ σε ασθενείς με Hodgkin και non-Hodgkin λεμφώματα

“…Η χορήγησή της, δε βελτίωσε την ταχύτητα και τη διάρκεια ανταπόκρισης καθώς και την επιβίωση ασθενών με προχωρημένο καρκίνο του μαστού. Παρόμοια αποτελέσματα έχουν βρεθεί και με τη μιτοξανδρόνη [199][200][201][202][203][204], την ιδαρουβικίνη [124,[205][206][207][208] και την πιραρουβικίνη [157,209]. Πρέπει εδώ να τονισθεί ότι οι συγκρίσεις που έχουν γίνει βασίζονται σε δόσεις που προκαλούν ισοδύναμη μυελοτοξικότητα με τη δοξορουβικίνη.…”