Abstract
Combinations of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) demonstrate synergistic antiproliferative activity in vitro. Therefore, we initiated a clinical study of recombinant TNF-alpha (rTNF-alpha) and rIFN-gamma combination therapy in humans. Twenty-five patients with metastatic cancer received both rTNF-alpha and rIFN-gamma by intramuscular injection for 5 consecutive days every 2 weeks for a total of 4 weeks. The dose levels were 5/5, 10/5, 10/10, 25/10, 25/25, 50/25, 50/50, 75/50, and 75/75 micrograms/m2 per day of rTNF-alpha/rIFN-gamma. A minimum of 2 patients were entered sequentially at each dose level. If the first 2-week cycle of therapy was well tolerated, the dose was increased to the next highest dose level during the second 2-week cycle. Fever, chills, and fatigue were observed at all doses. Severity of symptoms corresponded to increasing dose levels. Although TNF is identical to a molecule known as "cachectin," the vast majority of our patients did not lose weight while on study. However, alterations in lipid metabolism occurred and were manifested by a median change in triglyceride values of +40 mg/dl (range, -130 to +318 mg/dl), and in cholesterol values of -30 mg/dl (range, -103 t...Continue Reading
References
Sep 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·E A CarswellB Williamson
Aug 8, 1985·Nature·B BeutlerA Cerami
Apr 17, 1986·Nature·B Beutler, A Cerami
Jul 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·R KurzrockJ U Gutterman
Oct 1, 1986·The Journal of Experimental Medicine·R KurzrockJ U Gutterman
Apr 24, 1986·The New England Journal of Medicine·M TalpazJ U Gutterman
Sep 1, 1986·Nature·K TakedaK Konno
Feb 12, 1987·The New England Journal of Medicine·B Beutler, A Cerami
Oct 24, 1986·Science·K J TraceyJ D Albert
May 1, 1985·The Journal of Experimental Medicine·B BeutlerA Cerami
Nov 22, 1985·Science·B J SugarmanH M Shepard
Sep 1, 1980·Annals of Internal Medicine·J U GuttermanS Pestka
Aug 26, 1982·Nature·P W Gray, D V Goeddel
Dec 20, 1984·Nature·P W GrayL P Svedersky
Dec 20, 1984·Nature·D PennicaD V Goeddel
Nov 1, 1984·The New England Journal of Medicine·K A FoonJ Zeffren
Jan 5, 1984·The New England Journal of Medicine·J R QuesadaJ U Gutterman
May 5, 1983·The New England Journal of Medicine·S E KrownB Safai
Mar 6, 1986·Nature·H D HollandM McCaffrey
Nov 1, 1961·Clinical Pharmacology and Therapeutics·D A KARNOFSKY
Citations
Jan 1, 1991·Cancer Immunology, Immunotherapy : CII·L S MassadJ L Collins
Jan 1, 1991·Biotherapy·T Taguchi, Y Sohmura
Jun 8, 2000·Immunity·M K Slifka, J L Whitton
May 14, 2011·Experimental Biology and Medicine·Subash C GuptaBharat B Aggarwal
Jun 21, 2014·Future Oncology·Meaghan L KhanMitesh J Borad
Apr 1, 1992·International Journal of Immunopharmacology·J E Talmadge
Mar 1, 1990·Electrophoresis·M H BeresiniL B Epstein
Oct 1, 1992·Medical Hypotheses·R S Smith
Mar 4, 1999·Gynecologic Oncology·E R KostT J Herzog
Aug 1, 1995·Japanese Journal of Cancer Research : Gann·N SuzukiY Takakubo
Jun 28, 2016·Journal of Translational Medicine·Jing ShenChi Hin Cho
Oct 6, 2016·Carbohydrate Polymers·Woo Jung ShinYong Taik Lim
Sep 1, 1994·The British Journal of Surgery·E GaarH C Polk
Jan 15, 1992·Cancer·J H SchillerD R Spriggs
Jul 27, 2001·Cephalalgia : an International Journal of Headache·R H KemperG J Ter Horst
Sep 1, 1995·Anesthesiology·M P YeagerP M Guyre
Nov 1, 2011·Oncotarget·Nicholas J RobertsMatthias Holdhoff
Aug 19, 2017·Cell Chemical Biology·Juliane TotzkeEmily R Derbyshire
Jan 1, 1993·Medical Oncology and Tumor Pharmacotherapy·H F HavasM Goonewardene