Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study.
To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
van Gameren
M M
MM
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Willemse
P H
PH
Mulder
N H
NH
Limburg
P C
PC
Groen
H J
HJ
Vellenga
E
E
de Vries
E G
EG
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000628:therapy*; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity*; D007958:Leukocyte Count / Q000187:drug effects; D008175:Lung Neoplasms / Q000097:blood / Q000628:therapy*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010976:Platelet Count / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity
D016207:Cytokines; D006454:Hemoglobins; D015850:Interleukin-6; D011994:Recombinant Proteins; D002784:Cholesterol