Human pharmacological investigation of a human recombinant tumor necrosis factor preparation (PAC-4D) a phase-I trial

Abstract

15 patients aged between 24 and 66 years with 10 different malignant tumor diseases were treated with a recombinant human tumor necrosis factor preparation PAC-4D in a phase-I trial. The starting dose was 10(5) U PAC-4D as an intravenous short infusion. The maximally tolerable dose is around 18 X 10(5) U/m2. As the main clinical side effects were observed: fever, chills, hypertension with subsequent hypotension, lethargy, transient somnolence, headache, neurological deficiency symptoms, nausea and vomiting. Important laboratory-chemical parameters were the increase in transaminases and, in higher dose levels, leukocytosis with the left shift and lymphopenia in the differential blood picture. As dose-limiting toxicity are estimated hypotension, and neurological side effects and hepatotoxicity. In one female patient who received 27 X 10(5) U PAC-4D there appeared pronounced, histologically verified necroses in the metastases of a malignant fibrous histiocytoma.