Although various treatment methods have been applied to unresectable metastatic liver
tumors, an effective way to treat this disease has yet to be established. Recently, the combined treatment with
tumor necrosis factor-alpha (
TNF-alpha) and
melphalan has been reported to be effective in 75% of cases in Western countries. In the present study, the antitumor effect of isolated hypoxic hepatic perfusion (IHHP) with
TNF-SAM2 and an
anticancer agent (5-FU), which is widely used for
gastrointestinal cancers, was investigated using the F344 rat model with colonic liver
metastases. The inhibitory effect on
tumor growth in rats administered with either 40 microg/rat of
TNF-SAM2 (89%) or 5 mg/kg or 10 mg/kg of
5-FU (56% or 19%) was significantly greater than that in non-treated rats (176%). On the other hand, the inhibitory effect on
tumor growth in rats administered with both
TNF-SAM2 and
5-FU (10 mg/kg) was 65%, which was equal to, or less than, that in rats administered with only
TNF-SAM2 or
5-FU. There was no additive/synergistic effect of the combined treatment with these drugs. These results indicate the kinds and dose of
anticancer agents which, used in combination with TNF, need to be evaluated for the most appropriate antitumor effect in the IHHP method.