Intrahepatic arterial infusion of chemotherapy: pharmacologic principles.

Hepatic arterial (HA) infusional chemotherapy possesses a number of constraints not found with systemic chemotherapy. The drug used should have activity in a dose-responsive way without significant hepatic toxicity. The drug must also possess suitable pharmacokinetic properties, namely, a high total body clearance and hepatic extraction, so as to generate high hepatic and low systemic exposures. Of the drugs examined for HA use, 5-fluoro-2'-deoxyuridine (FUDR, floxuridine) demonstrates the best properties. In HA infusional therapy, the catheter is positioned to deliver drug directly to the liver only and must be connected to a reliable pumping mechanism. Surgical implantation of catheters and pumps provides a safe and reliable means to infuse HA FUDR. HA FUDR delivery via an implanted system in the treatment of colorectal liver metastases represents the largest application of HA therapy and provides a basis for future advances when combined with other regional and systemic treatments.