Study on avoiding method of infusion-site adverse events in chemotherapy with epirubicin and fosaprepitant employing immortalized human umbilical vein endothelial(HUEhT-1)cells and rats

Abstract

The combination of intravenous fosaprepitant dimeglumine (FAP, Proemend® I.V. Infusion), an antiemetic drug, and chemotherapy with anthracyclines such as epirubicin (EPI) can cause infusionsite adverse events. Avoiding method of infusion-site adverse events was studied in immortalized human umbilical vein endothelial (HUEhT-1) cells and rats. Cytotoxicity of FAP, EPI, diluted Proemend®, Tween 80 and a combination of FAP and EPI, and the effect of cell-surface washing after application of diluted Proemend® on cytotoxicity were studied in HUEhT-1 cells. In rats, the effect of infusion-site washing after FAP infusion was evaluated by measuring the intravascular accumulation of EPI in the combined use of FAP followed by EPI. FAP, EPI, and diluted Proemend® exhibited cytotoxicity concentration-dependently and marked synergistic cytotoxicity was observed between FAP and EPI. In HUEhT-1 cells, the washing of the cell surface after the application of FAP reduced the synergistic cytotoxicity significantly. In rats, the washing of the infusion site with saline after FAP infusion greatly decreased the intravascular accumulation of EPI infused thereafter. In conclusion, the washing of the infusion site by IV tube flushing after FAP infusion avoids the infusion-site adverse events due to the decrease in the vascular accumulation of EPI administered thereafter.