Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: Clinical and biologic effects

The authors evaluated the clinical and biologic effects of human recombinan t interleukin-6 (rhIL-6) in patients with refractory cancer. A phase I tria l using escalating doses of rhIL-6 (1-50 mu g (.) kg(-1 .) d(-1), Monday th rough Friday for 3 weeks) was performed in 30 patients. Toxicity was modera te and the maximum tolerated dose was determined to be 25 mu g (.) kg(-1 .) d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/mu L) in three patients. One patient wi th non-small-cell lung cancer had a partial response after three cycles of therapy. Thc biologic effects of rhIL-6 included anemia and dose-related th rombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes acid the CD14 (+)/CD35RB(+) +/- CD16C(+) mononuclear cell populations, These increases we re accompanied by increased levels of C-reactive protein, serum neopterin, and type I soluble tumor necrosis factor receptor. In contrast, rhIL-6 did not affect lymphocyte numbers or function (cytotoxicity, cytokine levels, i mmunoglobulin levels), with the possible exception of IL-2R alpha mRNA indu ction in peripheral blood lymphocytes, rhIL-6 has pleiotropic proinflammato ry actions in vivo and moderate toxicity when administered as long-term the rapy.