Adriamycin-induced heart failure: mechanisms and modulation

Adriamycin (doxorubicin) is one of the most effective chemotherapeutic agen ts against a variety of cancers, but its usefulness is seriously curtailed by the risk of developing heart failure. Available laboratory evidence sugg ests that an increase in oxidative stress, brought about by increased free radical production and decreased myocardial endogenous antioxidants, plays an important role in the pathogenesis of heart failure. Adriamycin-induced apoptosis and hyperlipidemia may also be involved in the process. Probucol, a lipid-lowering drug and an antioxidant, completely prevents the occurren ce of heart failure by reducing oxidative stress as well as by the modulati on of apoptis and high lipid concentrations. Thus, combined therapy with ad riamycin and probucol has a high potential for optimizing the treatment of cancer patients.