PHASE-I STUDY OF RECOMBINANT TUMOR-NECROSIS-FACTOR IN CANCER-PATIENTS
- 1 June 1987
- journal article
- research article
- Vol. 47 (11), 2986-2989
Abstract
Tumor necrosis factor is a cytokine derived from activated macrophages. This agent is cytostatic and cytolytic against transformed human cell lines in vitro and has in vivo activity against a variety of murine tumors. We report a clinical study of the pharmacokinetics, toxicity, and biological activity of i.v. and i.m. administered recombinant human tumor necrosis factor (rTNF). Twenty patients with metastatic cancer were given rTNF in doses ranging from 1 to 200 .mu.g/m2 by alternating i.m. and i.v. bolus injections with a minimal intervening period of 72 h. Each patient received a maximum of eight treatments given twice weekly over a 4-week period. With i.v. bolus administration, serum concentrations of rTNF were detected by enzyme-linked immunosorbent assay at doses of 25 .mu.g/m2 or greater. The clearance of rTNF in the serum was described by a monoexponential equation with a half-life calculated to be 14-18 min. After i.m. administration, serum concentrations of rTNF were consistently detected by enzyme-linked immunosorbent assay at doses of 150 .mu.g/m2 or greater. Peak concentrations were observed within 2 h and rTNF was occasionally detected, at the lower limit of sensitivity of the assay, at 24 h postinjection. rTNF was well tolerated clinically in this dose range, and there was evidence of antitumor effect.This publication has 14 references indexed in Scilit:
- Lipopolysaccharide-treated RAW 264.7 cells produce a mediator that inhibits lipoprotein lipase in 3T3-L1 cells.The Journal of Immunology, 1985
- Primary structure of human lymphotoxin derived from 1788 lymphoblastoid cell line.Journal of Biological Chemistry, 1985
- Human tumor necrosis factor. Production, purification, and characterization.Journal of Biological Chemistry, 1985
- PHARMACOKINETICS, SINGLE-DOSE TOLERANCE, AND BIOLOGICAL-ACTIVITY OF RECOMBINANT GAMMA-INTERFERON IN CANCER-PATIENTS1985
- Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activityNature, 1984
- Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude miceInternational Journal of Cancer, 1984
- Human tumor necrosis factor produced by human B-cell lines: synergistic cytotoxic interaction with human interferon.Proceedings of the National Academy of Sciences, 1983
- Inhibition of the growth and differentiation of erythroid precursor cells by an endotoxin-induced mediator from peritoneal macrophages.Proceedings of the National Academy of Sciences, 1983
- Recombinant Leukocyte A Interferon: Pharmacokinetics, Single-Dose Tolerance, and Biologic Effects in Cancer PatientsAnnals of Internal Medicine, 1982
- Lipoprotein lipase suppression in 3T3-L1 cells by an endotoxin-induced mediator from exudate cells.Proceedings of the National Academy of Sciences, 1982