Unresectable hepatocellular carcinoma (HCC) has a poor prognosis and little sensitivity to anticancer agents. We planned a combination immunotherapy, associating with rIL-2 continuous injection. Combination immunotherapy consists of 5 different biological response modifiers (BRM), i.e., rIL-2, OK-432, adriamycin (ADR), cyclophosphamide (Cy), and famotidine (Fa). rIL-2, OK-432 and ADR were administered from implantable infuser port connecting to a catheter which was injected into the hepatic artery via the gastroduodenal artery under laparotomy. OK-432, Cy, and Fa were also administered systemically. From 1988 to 1990, seven patients with unresectable HCC and two patients who underwent curative resection were treated by this therapy. The objective responses were evaluated by CT and angiography. This combination immunotherapy produced 3 cases of complete response and 2 of minor response. Immunological monitoring of lymphocyte subsets and NK activity of peripheral blood mononuclear cells was also performed. NK activity was significantly augmented and the percentage of Leu 7(-) NCD 16(+) cells increased during this therapy. Serious toxicity, but transient high fever and hypotension, was not observed during this therapy. All of these patients left the hospital within two weeks and returned to their previous job or similar life activity. These results suggest that this combination immunotherapy is worth performing in further clinical trials for hepatocellular carcinoma.

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