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- Title
A phase I clinical trial of recombinant human tumor necrosis factor.
- Authors
Creagan, Edward T.; Kovach, John S.; Moertel, Charles G.; Frytak, Stephen; Kvols, Larry K.; Creagan, E T; Kovach, J S; Moertel, C G; Frytak, S; Kvols, L K
- Abstract
We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF-alpha) in 27 patients with advanced solid neoplasms. Therapy consisted of a 30-minute intravenous (IV) infusion on days 1 through 5, every 2 to 3 weeks. Daily doses ranged from 5 micrograms/m2 to 200 micrograms/m2. Dose-limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38 degrees C) were not clearly dose-related between 5 micrograms/m2/d and 150 micrograms/m2/d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3, 1.2 X 10(3)/microliters in two patients) at a dose of 5 micrograms/m2/d and 150 micrograms/m2/d, respectively; and thrombocytopenia (leukocyte count, 73 X 10(3)/microliters) at 10 micrograms/m2/d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/microliters compared with a subsequent median of 462 cells/microliters. We also detected hypertriglyceridemia in all patients. The median baseline increased from 93 mg/dl (range, 56 to 219 mg/dl) to 203 mg/dl (range, 94 to 454 mg/dl). From our experience, a clinically manageable outpatient regimen for Phase II trials consists of rTNF-alpha (150 micrograms/m2) followed by a 1-hour IV infusion of 500 ml of normal saline to abrogate hypotension daily for 5 days every 2 weeks for four cycles, then every 3 weeks thereafter to facilitate recovery from constitutional sequelae.
- Subjects
TUMOR treatment; CLINICAL trials; COMPARATIVE studies; CLINICAL drug trials; HYPERLIPIDEMIA; LEUCOPENIA; RESEARCH methodology; MEDICAL cooperation; RECOMBINANT proteins; RESEARCH; RESEARCH funding; THROMBOCYTOPENIA; TUMOR necrosis factors; EVALUATION research
- Publication
Cancer (0008543X), 1988, Vol 62, Issue 12, p2467
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/1097-0142(19881215)62:12<2467::AID-CNCR2820621202>3.0.CO;2-5