P35 Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin in the paediatric population – a systematic literature investigation

Abstract

BackgroundIn cell line experiments, the selective NK-1-receptor antagonist Aprepitant was able to inhibit the cardiotoxic adverse effects of Doxorubicin,1 a common cytostatic used in paediatric cancer therapies. Cytostatic therapy is one of the principal reasons for toxic cardiomyopathy in children, resulting in dilated cardiomyopathy and consequently leading to heart failure. However, Aprepitant is currently licenced for adults and children and is indicated amongst others in the antiemetic supportive therapy of Doxorubicin regimes. To address the hypothesis of any indication of Aprepitant in preventing cardiotoxic adverse effects of Doxorubicin, systematic literature research is needed.MethodsSystematic literature research was examined using PubMed in January 2019. Selected inclusion criteria were: ‘Substance P’ or ‘Aprepitant’ and ‘Doxorubicin’/’cardiac inflammation’/’cardiomyopathy’ or ‘Aprepitant’ and ‘paediatrics’/’neonates’/’children’. The use of Aprepitant in adults and children as an antiemetic agent and the involvement of Substance P in (neurogenic) inflammation, cardiac infarction or diabetes led to the exclusion of publications.ResultsThe PubMed search resulted in 220 identified publications whereby 33 were relevant concerning the potential use of Aprepitant in the prevention of cardiotoxic adverse effects of Doxorubicin. It emphasises the potential use of Aprepitant in the prevention of toxic cardiomyopathy by antagonizing the inflammatory effects of the endogenous NK-1-agonist Substance P regarding cell and animal models.1 2 Based on these models, Substance P is associated with adverse cardiac remodelling and cardiac inflammation. However, in children, Aprepitant was only used as an antiemetic agent and no off-label indication was described.ConclusionSince toxic cardiomyopathy is a severe adverse effect in the Doxorubicin therapy in children, the evaluation of the role of Substance P is a promising and worthy approach to condense the knowledge about a potential use of Aprepitant in preventing paediatric toxic cardiomyopathy.ReferencesRobinson P, Kasembeli M, Bharadwaj U, et al. Substance P receptor signaling mediates doxorubicin-induced cardiomyocyte apoptosis and triple-negative breast cancer chemoresistance. Biomed Res Int2016; 2016. doi:10.1155/2016/1959270Levick SP, Soto-Pantoja DR, Bi J, et al. Doxorubicin-induced myocardial fibrosis involves the neurokinin-1 receptor and direct effects on cardiac fibroblasts. Heart Lung Circ. Published Online First: September 2018. doi:10.1016/j.hlc.2018.08.003Disclosure(s)Martin Feickert and Bjoern B. Burckhardt declare that there is no conflict of interest. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.