How to Improve the Safe and Effective Use of Doxorubicin in Children with Cancer

摘要: Doxorubicin, one of the anthracyclines, is a chemotherapeutic agent widely used to treat several pediatric cancers such as acute lymphocytic leukemia, myeloid Hodgkin lymphoma, non-Hodgkin softtissue sarcoma, bone Ewing neuroblastoma, and Wilms tumor. As such, this drug has contributed substantially dramatic improvement 5-year survival rates for many these childhood [1]. However, major potential adverse event use doxorubicin its cardiotoxicity. More than 50 % patients will develop asymptomatic cardiac dysfunction, whereas in six result clinical heart failure due cardiomyopathy [2]. The exact causative mechanism devastating is, despite fact that been decades patients, not fully elucidated. There more or less consensus about important role reactive oxygen species causing cell damage, progressive myocyte loss ultimately decreased contractility [3]. To date, risk factors have linked development doxorubicin-induced cardiotoxicity are higher single well total cumulative dose, irradiation, short infusion time duration, younger age, longer since treatment, female sex [4]. In addition, much recently, potentially genetic predictors brought our attention [5]. Multiple variants genes associated with identified [6]. until now, currently available knowledge both never resulted sufficient discriminatory power divide into groups high low developing issue journal, Voller colleagues described population pharmacokinetic model children which they function describe relation between clearance age [7]. They were able show, first time, pharmacokinetics (PK) infants cancer dependent. Clearly, finding might eventually assist designing tailored, safe, effective dosing regimen cancer. before demonstrated lower 3 years be change regimens cancer, there an absolute need only consider developmental PK but also, probably importantly, pharmacodynamics (PD). At glance, based on body clearance, it seems we group young reach same amount exposure compared older adolescents. what do really know dose-concentration-effect relationship 1 18 age? other words, urgent better This commentary refers article at doi:10.1007/s40262-015-0272-4.