TY - JOUR
T1 - Phase I trial intramuscularly administered tumor necrosis factor in patients with advanced cancer
AU - Jakubowski, A. A.
AU - Casper, E. S.
AU - Gabrilove, J. L.
AU - Templeton, M. A.
AU - Sherwin, S. A.
AU - Oettgen, H. F.
PY - 1989
Y1 - 1989
N2 - A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 μg/m2/d. Dose-limiting toxicities were encountered at doses > 100 μg/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses > 100 μg/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 μg/m2/d, administered for two courses.
AB - A phase I trial of intramuscularly administered recombinant human tumor necrosis factor (rTNF) was conducted in 19 adult patients with advanced solid tumors. The agent was administered daily for up to five consecutive days every other week for two to four courses. Doses of rTNF ranged from 5 to 200 μg/m2/d. Dose-limiting toxicities were encountered at doses > 100 μg/m2/d. Toxicities included tenderness, erythema and induration at the site of injection, fatigue, fever, chills, headache, anorexia, nausea, vomiting, and diarrhea. Moderate to marked reductions in WBC and platelet counts were observed regularly at the highest dose levels, but none were clinically significant. Hepatic enzyme elevation was seen frequently, and two patients developed hyperbilirubinemia. Only one of seven patients treated with doses > 100 μg/m2/d completed the planned course of therapy. Even at the highest dose levels, serum concentrations of rTNF could only rarely be detected in the serum. No therapeutic responses were observed. The maximal tolerated dose (MTD) of rTNF in this trial was 150 μg/m2/d, administered for two courses.
UR - https://www.scopus.com/pages/publications/0024503384
U2 - 10.1200/JCO.1989.7.3.298
DO - 10.1200/JCO.1989.7.3.298
M3 - Article
C2 - 2918329
AN - SCOPUS:0024503384
SN - 0732-183X
VL - 7
SP - 298
EP - 303
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -