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A great number of locoregional treatments are currently carried out to treat a variety of locoregional neoplastic diseases. Indications are the treatment of primary and metastatic liver tumors, peritoneal mesotheliomas, peritoneal spread of ovarian carcinomas, peritoneal recurrences of gastrointestinal cancers, peritoneal spread of retroperitoneal sarcomas, melanomas and sarcomas of the limbs, some primary tumors of the brain, breast, kidney, lung, bladder. But to deal with locoregional therapy demands to clarify some features of these malignancies. At this regard, the knowing of their natural history can be crucial to guide the choice of the correct locoregional treatment. For instance peritoneal carcinomatosis is considered as a main step of disease progression for ovarian cancer and often for gastrointestinal tumors as well. However when the tumors are confined on the surface of the peritoneum, basing on their own natural history, they can be considered as localized diseases. Selected patients with peritoneal neoplastic seeding, previously considered in a preterminal condition, can be considered as candidates for curative treatment, using cytoreductive surgical tecniques (16) and hyperthermic intraperitoneal chemotherapy (19). The same can be thought about others primary or metastatatic tumors when the neoplastic deposits are confined within a definite site or region of the body. In this paper the main aspects of liver metastases and peritoneal carcinomatosis natural history, two of the most frequently recognized indications for locoregional therapy, are presented.

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.

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).