山梨医科大学雑誌　第9巻4号　143-154(1994)

Optimal Dose of Continuous Interleukin-2 (IL-2) Infusion Together
with Intermittent Adriamycin Injection to the Hepatic Artery in
Advanced Hepatocellular Carcinoma Patients

Hidehiko IIZUKA, Masayuki YAMAMOTO, and Yoshiro MATSUMOTO

Abstract: To determine the appropriate hepatic arterial infusion dose of IL-2 to obtain long-lasting direct response in hepatocellular carcinorna (HCC), we analyzed deleterious factors after various intervals of direct tumor response to immunochemotherapy using adriamycin (ADR). The direct tumor response, survival rate, and changes in peripheral NK activity of 3 groups of advanced HCC patients were compared. Seventeen patients received continuous infusion of IL-2 (0.35×10^6 JRU/day) and intermittent injections of ADR emulsion (10mg) via the hepatic artery after cannulation. Six patients received IL-2 infusion for less than 6 months because of new lesions or side effects of IL-2 (IL-2 ineffective group), and 11 for more than 6 months (IL-2 + ADR group). Seven patients received the ADR emulsion therapy alone (ADR group). In the IL-2 + ADR group, excellent direct effect on liver tumors accompanied by increase in peripheral NK activity was observed. Four patients in the IL-2 + ADR group showed complete remission (CR) and 2 partial remission (PR) of liver tumors. However, long-term observation of NK activity revealed intractable decrease after the 6th to 8th month despite an increase in IL-2 dose, and the survival rate was not higher than that in the ADR group. The ADR group did not show increase of NK levels but 2 patients showed PR. This refractory decrease in the NK activity is probably due to changes of the immunological status following continuous high-dose infusion of IL-2. The appropriate dose for IL-2 infusion, which varies with changes in NK activity after CR is obtained, should be the minimum dose which maintains high NK activity in peripheral lymphocytes, so that rebound phenomenon is not induced.

Key words: Hepatocellular carcinoma, Interleukin-2, Adriamycin, Immunochemotherapy, Hepatic arterial infusion




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