Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: Pharmacokinetics, pharmacodynamics and immunomodulatory effects

This is the first report of the serum profile of a glycosylated recombinant form of human IL-6 (rhIL-6) administered subcutaneously (1-10 mu g/kg/day) in a phase I/II trial as a thrombopoietic agent in patients with advanced cancer, The pharmacodynamic effects of IL-6 were also examined, Detailed ph armacokinetic measurements were made in four patients. Peak concentrations at 5-8 h and a median t(0.5) of ca, 5 h were similar to those previously re ported for non-glycosylated IL-6. However, higher peak concentrations and a pparent differences in effective dose levels to those previously reported w ith the non-glycosylated form were seen. Indications of an apparent attenua tion in circulating IL-6 concentrations with continuing injections were see n in eight of 10 patients examined but anti-IL-6 antibody generation was se en in only two patients. Soluble interleukin 6 receptor concentrations gene rally decreased. No major changes in T cell subsets sere seen but expressio n of CD25 and CD54 by T lymphocytes significantly increased, accompanied by marked increases in soluble CD25 (sIL-2R) and CD54 (sICAM-1). No consisten t change in B cells, monocytes or NK cells sere seen. No evidence for induc tion of TNF-alpha was found, This study demonstrates similar biological eff ects of glycosylated rhIL-6 to those reported for the non-glycosylated form but illustrates several apparent differences which are discussed further. (C) 2000 Academic Press.