TREATMENT OF A HUMAN RENAL-CELL CARCINOMA IN NUDE-MICE WITH RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA AND ETOPOSIDE

The effect of treating a human renal cell adenocarcinoma xenografted i nto Balb/c-nu/nu (nude) mice with recombinant human tumor necrosis fac tor alpha (TNFalpha) and the cytostatic agent etoposide (ETP) as monot herapy or combination has been studied. Antitumor effects were evaluat ed by determining growth of the tumor implants by external caliper mea surements and tumor cell proliferation by determining the labelling in dex (LI) after pulse labelling with H-3-thymidine. The toxicity of the treatment with TNFalpha and/or ETP was also studied by measuring the animal weight. Monotherapy with TNFalpha had no effect on tumor growth or proliferation. Treatment with ETP as a single agent, TNFalpha plus ETP applied concurrently and TNFalpha plus ETP two days later led to a slight inhibition of tumor growth and also to a slight decrease of t he LI. In contrast to a monotherapy with TNFalpha, all therapeutic mod alities containing ETP showed an increased toxic effect on the animals represented by a distinct weight loss. This suggests that the minute efficacy of the treatment observed could well be due solely to its tox icity. In contrast to two other studies, no additive or synergistic ef fect of the antineoplastic activity of TNFalpha and/or ETP was found. The intertumoral variation of human renal cell carcinomas could be one reason for the different results with this therapeutic regimen.