Summary
Based on a phase I study in 1986, 22 patients have been entered in a phase II study of high-dose human tumor necrosis factor (rH-TNF) since May 1987. Of these patients, 18 are evaluable at present, 2 are still under investigation, and 2 have dropped out. All had advanced stages of cancer (9 soft-tissue sarcomas, 3 melanomas, 5 hypernephromas) and inclusion in the study was ethically acceptable (informed consent). The daily dose of rH-TNF was 15×105 units/m2, escalated to 21×105 units/m2 (683–956 μg/m2 every week; range 1–6 cycles). Additional prophylactic ketoprofen administration was carried out. Of the 18 evaluable patients, 4 responsed with no change (2/4, clinical improvement) and 14 showed progressive disease. The main toxicities observed were hypotension (decrease in systolic blood pressure, 21–60 Torr), leukocytosis, increases in ALAT/ASAT (WHO grade 0–4), fever (WHO grade 1–2), chills (mild to moderate), neurotoxicity (WHO grade 0–2), and nausea/vomiting (WHO grade 0–3).
This is a preview of subscription content, log in via an institution to check access.
References
Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B (1975) An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci USA 72: 3666–3670
Creaven PJ, Plager JE, Dupere S, Huben RP, Takita H, Mittelmann A, Proefrock A, (1987) Phase I clinical trial of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 20: 137–144
Kimura K, Taguchi T, Urushizaki I, Ohno R, Furue H, Hattori T, Ichihashi H, Inoguchi K, Majima H, Niitani H, Ota K, Saito T, Suga S, Suzuoki Y, Wakui A, Yamada K, for the A-TNF Cooperative Study Group (1987) Phase I study of recombinant human tumor necrosis factor. Cancer Chemother Pharmacol 20: 223–229
Lenk H, Tanneberger ST, Müller U, Ebert J, Shiga T (1988) Human pharmacological investigation of a human recombinant tumor necrosis factor preparation PAC-4D (Asahi) — a phase I trial and preliminary results of a phase II trial. Arch Geschwulsforsch 58 (2): 89–97
Tanneberger ST, Lenk H, Müller U, Shiga T (1987) Human pharmacological investigation of a human recombinant tumor necrosis factor preparation PAC-4D (Asahi) — a phase I trial. Immunobiology 175: 38
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lenk, H., Tanneberger, S., Müller, U. et al. Phase II clinical trial of high-dose recombinant human tumor necrosis factor. Cancer Chemother. Pharmacol. 24, 391–392 (1989). https://doi.org/10.1007/BF00257449
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00257449