[Systemic versus local therapy with recombinant tumor necrosis factor-alpha (r-TNF-alpha) in patients with advanced tumors].
44 patients with different advanced malignant tumors were treated with recombinant Tumor-necrosis factor alpha (rTNF-alpha) in two Phase-I trials. 30 patients received rTNF-alpha 3 x/week intramuscular in doses between 25-300 mcg. 14 patients were treated intra/peritumoral with rTNF-alpha in the same dose range. The maximal tolerated dose (MTD) was 150 mcg/m2 for both ways of application. The duration of therapy was 1-26 weeks for systemic application and 2-20 weeks for local treatment. 25 patients treated systemically were evaluable for response. In 2 patients a minor response (MR) and in 9 patients stable disease was observed. 5/14 patients receiving rTNF-alpha locally showed a significant tumor regression (3 PR, 2 MR). Main side effects were dose dependent fever, chills, anorexia and nausea. In doses greater than 50mcg/m2 a decrease of blood pressure according to WHO III was noted. Hematologic toxicity included a transient decrease of leucocytes and platelets without indicating a cumulative hematologic toxicity. There were no further organ toxicities. The experience from both phase-I trials indicate a definite antitumoral activity of rTNF-alpha suggesting that locoregional treatment might be superior to systemic application. The side effects observed might be a limitation for larger clinical trials.
Bartsch
H H
HH
Abteilung Hämatologie/Onkologie, Universität Göttingen.
Pfizenmaier
K
K
Schröder
M
M
Nagel
G A
GA
D000328:Adult; D000368:Aged; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007267:Injections; D007273:Injections, Intramuscular; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000009:adverse effects
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha
Systemische versus lokale Therapie mit rekombinantem Tumor-Nekrose-Faktor-alpha (r-TNF-alpha) bei Patienten mit fortgeschrittenen Tumoren.