Adriamycin-induced myocardial toxicity: new solutions for an old problem?
Adriamycin is a potent and broad-spectrum antineoplastic agent that plays a major role in cancer chemotherapy. Unfortunately, its use has been hampered by conventional toxicities and cardiotoxicity manifested by congestive cardiomyopathy. Adriamycin is particularly toxic to heart tissue and constitutes a major cause of morbidity and mortality due to its complex pathogenesis. In this review, the different forms of cardiotoxicity produced by adriamycin as well as the biochemical changes induced by this drug are summarized. Secondly, the current hypotheses proposed to explain adriamycin-induced myocardial damage (the iron and free-radical hypothesis, the metabolic hypothesis, the "unifying hypothesis" and apoptosis) and the attempts to reduce adriamycin-induced myocardial toxicity are discussed (e.g. dose limitation, close cardiac monitoring, alteration of dosage schedules, development of new anthracycline analogs, and the administration of protective agents and liposomal encapsulation). Finally, we summarized our own experimental and clinical experience in ameliorating and or preventing adriamycin-induced cardiotoxicity and the latest attempts to prevent and/or monitor cardiac function. According to this, a combination of usual doses of calcium antagonist drugs plus vitamins A and E seems advisable.
Outomuro
Delia
D
Instituto de Investigaciones Cardiológicas, Universidad de Buenos Aires-Conicet, Argentina.
Grana
Daniel R
DR
Azzato
Francisco
F
Milei
José
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D004341:Drug Evaluation / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin