Epirubicin and its metabolites levels in experimental liver metastases after different administration routes.

Locoregional chemotherapy in the 80's was considered an effective palliative treatment for unresectable hepatic metastases. With the advent of new drugs supporting effective systemic chemotherapy it was disregarded for many years. Recently, following the advent of new drugs and the developing of new association scheme, it has regained interests also for its adjuvant and neoadjuvant role to hepatic resections. Current schemes of locoregional and systemic chemotherapy for liver metastases are based on continuous infusions using implantable pumps but confirmation, in term of tissue drug concentration, that continuous infusions do better than bolus infusions is still lacking. To address this specific aspect we have experimentally compared these two different administration modalities using an anthracyclin, Epiadryamicin (EPI), with high plasmatic clearance and main biliary escretion (8,16) and infused through arterial, portal and systemic routes. The most high EPI concentration within the tumour was obtained after bolus-arterial infusion but also for continuous infusions the artery resulted better than other routes. Differently the most high EPI liver concentration resulted after portal infusion both if infused with a bolus or in 5 minutes time. This experiment may therefore legitimate the clinical use of this drug with bolus repeated infusions through the hepatic artery.