A Clinical-Pharmacological Evaluation of Hepatic Arterial Infusion of Adriamycin1

We have evaluated the degree to which hepatic arterial infusion of Adriamycin produces higher hepatic and lower systemic drug concentrations than are achieved with corre sponding peripheral venous infusion. Hepatic arterial catheters were placed in seven patients with primary or metastatic liver cancer. Temporary hepatic venous catheter placement allowed direct sampling of drug levels in the hepatic venous effluent. Adriamycin and metabolites were measured by a highly sensi tive, unambiguous, high-performance liquid Chromatographie system with sensitivity in the 2to 10-pmol/sample range. Hepatic extraction of Adriamycin was demonstrated with an extraction ratio (hepatic arterial level minus hepatic venous level/hepatic arterial level) of 0.45 to 0.50, depending upon the dosage of Adriamycin chosen. The systemic Adriamycin levels during hepatic arterial infusion were 25% lower than the corresponding systemic levels with peripheral venous infusion. Hepatic venous anthracycline levels, which are one measure of intrahepatic drug concentration in the hepatic and tumor capillary bed, were consistently higher when drug was given by the hepatic arterial route. Plasma levels of Adriamycin correlated well with the subsequent development of myelosuppression. Four of five patients with breast adenocarcinoma metastatic to the liver demonstrated significant tumor regression lasting 1 to 7 months. A clinical complete response was seen in one patient, and three demonstrated partial responses. One of two patients with primary adenocarcinoma of the bile duct achieved a partial response lasting 1 month. These results support hepatic arterial infusion as a means to improve the therapeutic index of Adriamycin and provide a sound pharmacological justification for its use in the treatment of cancer of the liver. This therapeutic modality may best be suited for the treatment of those metastatic tumors of the liver which are known to respond to Adriamycin administered sys-