Anti-tumor effect of recombinant murine TNF-alpha (rMuTNFa) given by continuous i.v. infusion as compared to repeated i.v. injections in a rat liver metastasis model.

Anti-tumor effects of TNF in animal models are well documented. Therapeutic use of TNF, however, is hampered by its toxicity. In rats a single intravenous (i.v.) injection of 40 micrograms/kg is lethal. When given by continuous i.v. infusion, much higher doses are well tolerated. To compare the therapeutic efficacy of rMuTNF given either as repeated i.v. injections or as a continuous infusion, we have used a liver metastasis model (tumor CC531). The number of liver metastases at day 28 after tumor inoculation served as a parameter. The route of administration, administration schedule and dose, did, in general, not influence the effect produced by rMuTNFa. Only early continuous infusion had an effect on the number of liver metastases. A sublethal dose, given as a late continuous infusion, had no significant effect. It thus appears that rTNFa, even when administered at high doses, is not a very efficient anti-tumor agent. Attention should rather be focused on the use of rTNFa in combination with other substances, for example, interferons.