Antitumor effects of isolated hypoxic hepatic perfusion (IHHP) with high-dose TNF against colonic liver metastases in a rat model.

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.