Can Anthracycline Therapy for Pediatric Malignancies Be Less Cardiotoxic?

Abstract

Anthracyclines have a central role in the treatment of cancer in pediatric patients but confer an increased risk of cardiac dysfunction. Several strategies have been employed to help reduce anthracycline-induced cardiotoxicity, including pretreating the patient with the iron chelator dexrazoxane and infusing the dose of anthracycline over a longer period. Much focus has also been placed on the development of methods that decrease the toxicity of parent compounds, specifically through the use of drug carriers such as liposomes, and on the development of new, potentially less toxic anthracycline derivatives, such as amrubicin and pixantrone. We provide a review of these strategies, focusing on studies in pediatric patients when available, and support the idea that anthracycline therapy can be less cardiotoxic in pediatric patients.

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

“…Reducing plasma concentrations of free doxorubicin is also believed to reduce cardiotoxicity. 474 Currently, the only liposomal doxorubicin approved by the US Food and Drug Administration is Doxil, a pegylated liposomal doxorubicin. 474 Pegylated liposomal doxorubicin reduces the overall risk of cardiotoxicity compared with conventional doxorubicin.…”

“…474 Currently, the only liposomal doxorubicin approved by the US Food and Drug Administration is Doxil, a pegylated liposomal doxorubicin. 474 Pegylated liposomal doxorubicin reduces the overall risk of cardiotoxicity compared with conventional doxorubicin. 475 Although further research is required to fully understand the effect of liposomal-encapsulated anthracyclines in children, biopsy samples have shown that this structural modification lowers the chance of early cardiotoxicity without compromising the antineoplastic activity of conventional anthracycline.…”

“…482 Epirubicin was less toxic to cardiomyocytes than was doxorubicin at equimolar doses, but it increased cardiotoxicity slightly when administered at equally myelotoxic doses. 474,482 Idarubicin is a structural analog of daunorubicin, another common anthracycline. Its C-methoxyl group in the D ring is replaced with a hydrogen moiety that is less cardiotoxic than daunorubicin.…”

“…Other methods that are independent of oxidative stress, such as DNA mutation mitigation, may mediate the cardiac protection involved with iron chelation. 474,491 These discoveries have led to a great deal of interest in the cardioprotective effects of dexrazoxane 489,490 ; however, concern has arisen over whether dexrazoxane might increase the risk of second malignancies by reducing the antineoplastic effect of doxorubicin. Several studies have not found an association (Figure 3), 22,493,494 but one did, 495 although its findings have been questioned.…”

Doxorubicin-Induced Oxidative Injury of Cardiomyocytes - Do We Have Right Strategies for Prevention?

“…Thus, the changes in tissue distribution of liposomal DOX www.intechopen.com lead to less drug exposure in sensitive organs. The ability to reduce the plasma levels of free DOX is probably the source of the reduced cardiotoxicity provided by its liposomal formulation (Fulbright et al, 2010). Also, the release of drug is slow, which may avoid high peak plasma concentrations.…”