From the Department of Pediatric Oncology and the Late Effects Outpatient Clinic (PLEK: Polikliniek Late Effecten Kindertumoren) and Study Group, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Elvira C. van Dalen, MD, PhD, Department of Pediatric Oncology, Room F8-257, Emma Children's Hospital/Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; e-mail: e.c.vandalen{at}amc.uva.nl
Overview: Anthracyclines have gained widespread use in the treatment of childhood cancer. Unfortunately, their use is limited by a dose-dependent cardiotoxicity, which is a prevalent problem. Prevention is thus essential and different methods have been pursued, including the use of regimens featuring lower cumulative anthracycline doses, cardioprotective agents, and potentially less cardiotoxic anthracycline analogs and dosing schedules. This article reviews the evidence evaluating the effect of anthracycline dosing schedules on cardiac function and summarizes recommendations for future research. Only two randomized, controlled pediatric trials evaluated the effect of different infusion durations (i.e., 48 hours compared with bolus) on cardiotoxicity. Both studies failed to identify a difference in cardiotoxicity among patients randomly assigned to receive continuous, compared with bolus, anthracycline infusions. However, a meta-analysis of four randomized studies in adults showed a statistically significant lower rate of clinical heart failure among patients who received anthracycline by infusion duration of 6 hours or longer, compared with those patients who received a shorter anthracycline infusion duration. Pooling of results to evaluate the effect of infusion duration on the risk of asymptomatic cardiac dysfunction was not possible, but, in individual studies, the 6 hours or longer infusion duration also seemed to reduce the risk of asymptomatic cardiac damage. No data on different anthracycline peak doses, defined as the maximum dose received in 1 week, were available. Evidence of a benefit of different anthracycline dosing schedules in preventing cardiotoxicity in children is still lacking. Because there is only a small amount of available data for children and it is risky to extrapolate adult data to children, more research is needed to establish the exact role of different infusion durations in preventing anthracycline-induced cardiotoxicity in children.
