Liposomal anthracyclines for improved cardiac tolerability

Anthracyclines are amongst the most utilized antitumour agents. However, their clinical utility is limited by a cumulative and potentially life-threatening form of cardiotoxicity. Several strategies have been devised to circumvent these adverse effects, including the development of less toxic analogues, liposomal encapsulation, alterations in scheduling and the addition of cardioprotectant agents. Although prolongation of the application of anthracyclines can reduce the risk of cardiomyopathy, practical considerations especially the need for central venous access and/or portable infusion devices limit the clinical use. Epirubicin, a semisynthetic derivative of doxorubicin, has a lower cardiotoxic potential. However, the definition of the equivalent dose compared to doxorubicin remains controversial. Liposomal encapsulation alters pharmacokinetic properties of anthracyclines. Reduced free drug concentrations in plasma results in an improved therapeutic index and may decrease the risk of cardiomyopathy. Myocet™, a conventional liposomal formulation of doxorubicin, has been shown within randomized trials to be equally effective compared to doxorubicin and is associated with a significantly lower risk of cardiotoxicity. The pegylated liposomal doxorubicin Caelyx®, seems to have a low cardiotoxic potential, but randomized trials comparing conventional doxorubicin and Caelyx are currently not available. The cardioprotective agent dexrazoxane significantly reduces anthracycline-induced cardiotoxicity but might interfere with the antitumour activity.