Recombinant human tumor necrosis factor administered as a 24-hour intravenous infusion. A phase I and pharmacologic study
DR Spriggs, ML Sherman, H Michie… - JNCI: Journal of the …, 1988 - academic.oup.com
DR Spriggs, ML Sherman, H Michie, KA Arthur, K Imamura, D Wilmore, E Frei III, DW Kufe
JNCI: Journal of the National Cancer Institute, 1988•academic.oup.comRecombinant human tumor necrosisj factor (rH-TNF) is a cytokine with direct antitumor
properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of
115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 μg of rH-TNF/m2.
Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the does of
rH-TNF administered. Doses> 454 μg/m2 frequently caused severe lethargy and fatigue,
which precluded hospital discharge of the patient at the completion of therapy. The dose …
properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of
115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 μg of rH-TNF/m2.
Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the does of
rH-TNF administered. Doses> 454 μg/m2 frequently caused severe lethargy and fatigue,
which precluded hospital discharge of the patient at the completion of therapy. The dose …
Abstract
Recombinant human tumor necrosisj factor (rH-TNF) is a cytokine with direct antitumor properties. In a phase I trial we continuously infused rH-TNF for 24 hours. We gave a total of 115 courses of therapy to 50 patients. Doses ranged from 4.5 to 645 μg of rH-TNF/m2. Systemic toxicity, including fever, chills, fatigue, and hypotension, increased with the does of rH-TNF administered. Doses >454 μg/m2 frequently caused severe lethargy and fatigue, which precluded hospital discharge of the patient at the completion of therapy. The dose-limiting toxicity was gypotension, and five patients treated at the two high3est dose levels requirede dopamine treatment. Other organ-specific toxicity was modest and spontaneously resolved after 48hours. The24-hour infusions of rH-TNF were associated weith significant decreases in serum cholesterol and high-density lipoprotein levels. Pharmacokinetic studies using an enzyme-linked immunosorbent assay demonstrated peak plasma rH-TNF levels of 90-900 pg/mL. Despite continuous infusion of rH-TNF. no steady-state level was achieved. The recommended phase II dose for rH-TNF as a 24-hour continuous infusion is 545 μg/m2. [Natl Cancer Inst 1988;80:1039–1044]
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