Recent advances in the prevention of anthracycline cardiotoxicity in childhood

The prevention of anthracycline cardiotoxicity is particularly important in children who can be expected to survive for decades after cancer chemother apy with these agents. The rapid increase in clinical toxicity at doses gre ater than 550 mg/m(2) of doxorubicin (DOX) has made this dose the limiting one in order to avoid DOX-induced cardiac failure. However, arbitrary dose limitation is inadequate because of variability of individual tolerance. De creasing myocardial concentrations of anthracyclines (ANT) and their metabo lites and schedule modification of administration can reduce anthracycline cardiotoxicity. Anthracycline structural analogues such as epirubicin, idar ubicin and mitoxantrone have been used in clinical practice. In addition, t he liposomal ANT, which can be incorporated into a variety of liposomal pre parations, are a new class of agents that may permit more specific organ ta rgeting of ANT, thereby producing less cardiac toxicity. Much interest has focused on the administration of ANT in conjunction with another agent that will selectively attenuate the cardiotoxicity. As is known, the ANT chelat e iron and the DOX-iron complex catalyzes the formation of extremely reacti ve hydroxyl radicals. Many agents, such as dexrazoxane (DEX), able to remov e iron from DOX, have been investigated as anthracycline cardioprotectors. Clinical trials of DEX have been conducted in children and significant shor t-term cardioprotection with no evidence of interference with antitumor act ivity has been demonstrated. Whether long-term cardiac toxicity will also b e avoided in surviving patients has not yet been determined.