Hepatic arterial infusion of interleukin-2 in advanced hepatocellular carcinoma

From August 1988 to February 1991, we performed hepatic arterial cannulation after tumor mass reduction in 17 patients with advanced hepatocellular carcinoma. By a subcutaneous infusion pump the patient received a continuous infusion of interleukin-2 (IL-2) (0.35 x 10(6) Japanese Reference Unit/day) and intermittent chemoembolization with 10 mg doxorubicin emulsion. The longest period of IL-2 infusion was 32 months. In 3 patients, the IL-2 dose could not be increased to the planned level due to fever or jaundice. Eight patients received the infusion for more than 10 months. NK and LAK activity in the peripheral blood, which had been reduced after partial liver resection, arterial embolization, or ethanol injection, was enhanced significantly by the IL-2 infusion, and the levels remained high for about 8 to 10 months. During periods of high NK and LAK activity, direct effects on the liver tumors were observed. In 11 patients who received IL-2 infusion for more than 6 months there was CR in 4, PR in 2, NC in 3 and PD in 2. Thereafter, however, the levels of NK and LAK activity decreased despite increase in the IL-2 dose, and sudden appearance of metastatic tumors caused deterioration of the patients. The 1-year and 2-year cumulative survival rates were 41% and 16% respectively. Further studies are required to explore ways for longer-lasting enhancement of NK and LAK activity.