The importance of patient monitoring in clinical cytokine trials: use of serum markers to define biologically active doses.
Due to their pleiotropic activities, network-like interactions, unknown mode of action and peculiar pharmacokinetics, the in vivo application of cytokines in clinical therapy studies is a difficult task. This paper deals with two therapeutic strategies which imply either maximum tolerated or biological active doses of human recombinant cytokines. Evidence is presented that the serum markers beta-2-microglobulin, which relates to HLA-AB antigen biosynthesis, and neopterin, which relates to macrophage activation, are useful response parameters for the definition of biological activity of IFN-alpha and IFN-gamma. Defined by such means, biological active doses are shown to be considerably less toxic than maximum tolerated doses, but are equally or more effective in the treatment of certain malignant disease states.
Huber
C
C
Department of Internal Medicine, University of Innsbruck, Austria.
Herold
M
M
D015415:Biomarkers / Q000097:blood*; D001708:Biopterins / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000008:administration & dosage*; D008991:Monitoring, Physiologic / Q000379:methods*; D009369:Neoplasms / Q000628:therapy*; D019798:Neopterin; D011994:Recombinant Proteins / Q000008:administration & dosage; D001613:beta 2-Microglobulin / Q000378:metabolism
D015415:Biomarkers; D007370:Interferon Type I; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; D001708:Biopterins; D019798:Neopterin; D007371:Interferon-gamma