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A phase I clinical trial of recombinant human tumor necrosis factor
Author(s) -
Creagan Edward T.,
Kovach John S.,
Moertel Charles G.,
Frytak Stephen,
Kvols Larry K.
Publication year - 1988
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19881215)62:12<2467::aid-cncr2820621202>3.0.co;2-5
Subject(s) - medicine , leukopenia , regimen , gastroenterology , hypertriglyceridemia , chills , surgery , toxicity , cholesterol , triglyceride
We performed a Phase I assessment of recombinant human tumor necrosis factor (rTNF‐α) 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 μg/m 2 to 200 μg/m 2 . Dose‐limiting sequelae were hypotension, rigors, and phlebitis. Transient fatigue and fever (median, 38°C) were not clearly dose‐related between 5 μg/m 2 /d and 150 μg/m 2 /d. Other reversible complications in three patients included transient leukopenia (leukocyte count, 1.3,1.2 × 103/μl in two patients) at a dose of 5 μg/m 2 /d and 150 μg/m 2 /d, respectively; and thrombocytopenia (leukocyte count, 73 × 10 3 /μl) at 10 μg/m 2 /d. Among 22 patients with initial and subsequent differential counts, the median number of eosinophils at the commencement of therapy was 182 cells/μl compared with a subsequent median of 462 cells/μl. 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‐α (150 μg/m 2 ) 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.