ISOLATED HEPATIC PERFUSION WITH TUMOR-NECROSIS-FACTOR AND MELPHALAN FOR UNRESECTABLE CANCERS CONFINED TO THE LIVER

Purpose: To evaluate the efficacy and systemic and regional toxicities of hyperthermic isolated hepatic perfusion (IHP) using tumor necrosis factor (TNF) and melphalan for the treatment of unresectable primary or metastatic cancers confined to the liver. Patients and Methods: Thi rty-four patients (18 men and 16 women; mean age, 49 years) underwent a 60-minute hyperthermic (39.5 degrees to 40.0 degrees C) IHP performe d by laparotomy that used TNF 1.0 mg and melphalan 1.5 mg/kg. Perfusio n inflow was through the gastroduodenal artery and outflow was from a cannula positioned in an isolated segment of retrohepatic inferior ven a cava (IVC). Infrahepatic IVC and portal venous blood flow were shunt ed to the axillary vein using an external venoveno bypass circuit. Com plete vascular isolation of the liver was confirmed by an I-131-labell ed human serum albumin monitoring technique. Results: There was no ope rative mortality. Seventy-five percent of patients had reversible grad e III or IV (National Cancer Institute Common Toxicity Criteria) hepat ic toxicity with one treatment-related mortality (3%) because of hepat ic venoocclusive disease. In 33 assessable patients, the overall respo nse rate was 75% (complete response, one patient [3%]; partial respons e, 26 patients [72%]). With ct median potential follow-up of 15 months , the mean duration of response was 9 months (range, 2 to 30 months). Conclusion: IHP with TNF and melphalan results in significant regressi on of bulky hepatic cancers confined to the liver in the majority of p atients. Based on these initial results, further refinement of this tr eatment technique is warranted; perhaps by the combination of IHP with other regional treatment strategies to provide long-term control of u nresectable cancers confined to liver. (C) 1998 by American Society of Clinical Oncology.