Determination of antineoplastic activity and toxicity of tumor necrosis factor (TNF) in animal experiments. Correlation to clinical findings.
Because of the deep evolutionary roots which macrophages and their products have, it should be possible to relate effects of the biological response modifier TNF observed in cancer patients with those determined in animal species. We have tested this hypothesis both with regard to antitumor efficacy and unwanted side-effects in murine tumor models. In the intramuscularly (i.m.) transplanted B16 melanoma, TNF had both after intratumoral (i.t.) and intravenous (i.v.) administration (qd 7-11, 14-17) a significant and dose-dependent effect on tumor growth. This effect was transitory and led only to a moderate increase in survival time of the animals. This correlates well with the also unsatisfactory clinical antineoplastic activity of TNF. From the measurement of body weight reduction, WBC counts, platelets, recalcification time, transaminases and body temperature in tumor bearing mice it can be concluded that there are close similarities to the side-effects observed in patients, although the level and/or time course of the noticed changes were differently expressed. In principle, it seems possible to predict clinical effects of biological response modifiers in animal experiments even if not all mechanisms are clearly understood.
Fichtner
I
I
Academy of Sciences of GDR, Central Institute of Cancer Research, Berlin-Buch.
Lemm
M
M
Becker
M
M
Tanneberger
S
S
D000818:Animals; D000970:Antineoplastic Agents; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha