title: Phase 1 trial of subcutaneous IL-6 in patients with refractory cancer: clinical and biologic effects.
abstract: The authors evaluated the clinical and biologic effects of human recombinant interleukin-6 (rhIL-6) in patients with refractory cancer. A phase 1 trial using escalating doses of rhIL-6 (1-50 microg x kg(-1) x d(-1), Monday through Friday for 4 weeks) was performed in 30 patients. Toxicity was moderate and the maximum tolerated dose was determined to be 25 microg x kg(-1)x d(-1) based on cardiac and neurocortical toxicity in one patient each and thrombocytosis (platelets > 800,000/microL) in three patients. One patient with non-small-cell lung cancer had a partial response after three cycles of therapy. The biologic effects of rhIL-6 included anemia and dose-related thrombocytosis. Various proinflammatory activities were induced and included dose-related cyclical increases in peripheral blood monocytes and the CD14+/CD45RB+ +/- CD16C+ mononuclear cell populations. These increases were 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, immunoglobulin levels), with the possible exception of IL-2Ralpha mRNA induction in peripheral blood lymphocytes. rhIL-6 has pleiotropic proinflammatory actions in vivo and moderate toxicity when administered as long-term therapy.
authors.affiliation: Experimental Therapeutics Program, The Cleveland Clinic Cancer Center, USA.
authors.forename: T
authors.initials: T
authors.lastname: Olencki
authors.forename: J
authors.initials: J
authors.lastname: Finke
authors.forename: R
authors.initials: R
authors.lastname: Tubbs
authors.forename: P
authors.initials: P
authors.lastname: Elson
authors.forename: D
authors.initials: D
authors.lastname: McLain
authors.forename: P
authors.initials: P
authors.lastname: Herzog
authors.forename: G T
authors.initials: GT
authors.lastname: Budd
authors.forename: H
authors.initials: H
authors.lastname: Gunn
authors.forename: R M
authors.initials: RM
authors.lastname: Bukowski
mesh_terms: D000210:Acute-Phase Reaction; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000187:drug effects; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018579:Patient Selection; D011336:Probability; D012008:Recurrence; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D015850:Interleukin-6