Epiadryamicin concentration in experimental hepatic metastases after bolus or continous infusion through systemic or locoregional routes.
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abstract
Locoregional chemotherapy in the 80's was considered an effective palliative treatment for unresectable hepatic metastases: it significantly improved the response rates if compared with systemic chemotherapy but didn't modify the survival (7,19). 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 (1,2,3,9,13,14,15,18). Loco-regional drug administration is feasible through two different administration routes, portal system and hepatic artery; the hepatic arterial infusion, in terms of tumor tissue antiblastic concentration, seems to be the most effective (6) Current schemes of chemotherapy for liver metastases are based on continuous infusions using implantable pumps (11, 12) 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).