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 into Balb/c-nu/nu (nude) mice with recombinant human tumor necrosis factor alpha (TNF alpha) and the cytostatic agent etoposide (ETP) as monotherapy or combination has been studied. Antitumor effects were evaluated by determining growth of the tumor implants by external caliper measurements and tumor cell proliferation by determining the labelling index (LI) after pulse labelling with 3H-thymidine. The toxicity of the treatment with TNF alpha and/or ETP was also studied by measuring the animal weight. Monotherapy with TNF alpha had no effect on tumor growth or proliferation. Treatment with ETP as a single agent, TNF alpha plus ETP applied concurrently and TNF alpha plus ETP two days later led to a slight inhibition of tumor growth and also to a slight decrease of the LI. In contrast to a monotherapy with TNF alpha, all therapeutic modalities 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 toxicity. In contrast to two other studies, no additive or synergistic effect of the antineoplastic activity of TNF alpha 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.