Objective: To determine the maximally tolerated dose and associated toxicity of r-γ-IFN. In addition, to evaluate the development of serum IFN neutralizing factors. Design: This is an open-labeled, Phase I dose escalating trial.
Setting: This trial was carried out at a Veteran's Administration and Army hospital.
Patients: Patients with advanced malignancies for whom no known effective therapy is available were eligible. Patients must have adequate organ function, a performance status of 2 or lower and a minimal life expectancy of 2 months.
Intervention: Patients received escalating doses of r-γ-IFN (0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 X 106 IU/m2) daily for 5 days given intravenously over 2 hours every other week.
Main Outcome Measures: Tumor response was followed clinically, with radiographic support when appropriate. Toxicity was evaluated using the World Health Organization (WHO) standard toxicity grading guidelines. Serum samples were used to monitor and evaluate the IFN neutralizing factors.
Get full access to this article
View all access options for this article.
References
1.
Bordon EC, Fall LAInterferons: biological, cell growth, inhibitory and immunological effects . Prog Hematol.1981;1:641.
2.
Brarca AA, Baglioni C.Evidence that type I and type II interferons have different receptors. Nature. 1981;294:768-770.
3.
Blalock JE, Georgiades MP, Langford MP, et al. Purified human interferon has more potent anticellular activity than fibroblast or leukocyte interferon. Cell Immunol.1980;49:390-394.
4.
Rubin BY, Gapta SLDifferential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. Proc Natl Acad Sci.1980;77: 5928-5932.
5.
Basham T., Merigan TCImmunoregulation by gamma-interferon ?Nature. 1982;299:778-782.
6.
Vilcek J., Gray PW, Rinderknecht E., et al. Interferon-gamma: A lymphokine for all seasons. In: E. Pick (ed), Lymphokines, Vol. 12. Orlando: Academic Press, 1984.
7.
Perussia B., Dayton ET, Lazarus R., et al. Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway. J ExpMed.1983;158:2058-2080.
8.
Sidman CL, Marshall JD, Shultz LD, et al. Gamma interferon is one of several direct B cell maturing lymphokines . Nature.1984;309:801-803.
9.
Gutterman JU , Rosenblum MG, Rios A., et al. Pharmacokinetic study of partially pure γ-interferon in cancer patients. Cancer Res.1984;44:4164-4171.
10.
Sherwin SA, Foon KA, Abrans PG, et al. A preliminary phase I trial of partially purified interferon-γ in patients with cancer. J Biol Response Mod.1984;3: 599-607.
11.
Speigel RJ, Spicehandler JR, Jabobs SL, Oden EMLow incidence of serum neutralizing factors in patients receiving recombinant alpha-2b interferon (Intron-A). Am J Med.1986;80:223-228.
12.
Vadham-Raj S. , Al Katib A., Bhalla R., et al. Phase I trial of recombinant interferon gamma in cancer patients. J Clin Oncol.1986 ;4:137-146.
13.
Vadham-Raj S. , Natham CF, Sherwin SA, et al. Phase I trial of recombinant interferon gamma by 1-hour IV infusion. Cancer Treat Rep.1986;70: 609-614.
14.
Data on file, Schering Corp., Kenilworth, NJ, 07033.
15.
Brown TD, Koeller J, Boengher, Golanda J., Bonnem EM, Spiegel RJ, VonHoff DD. A Phase I trial of Recombinant DNA Gamma Interferon. J Clin Oncol.1987;5:790-798.
16.
Quesada JR, Talpaz M., Rios A., et al. Clinical toxicity of interferons in cancer patients: A Review . J Clin Oncol.1986;4:234-243.
17.
Mattson K., Niiragen A., Iivanzinen M., et al. Neuro-toxicity of Interferons. Cancer Treat Rep.1983;67: 958-961.
18.
Friess G., Brown T., Boyd J., et al. Cardiac Rhythm Effects of Gamma Interferon. Proc Am Soc Clin Oncol.1986;5:225.
19.
Kurzrock R. , Quesada JR, Talpox M., et al. Phase I Study of Multiple Dose Intramuscularly Administered Recombinant Gamma Interferon. J Clin Oncol.1986;4:1101-1109.
20.
VanderBurg M., Edelstein M., Geril L., et al. Recombinant Interferon g (Immuneron) Results of a Phase I Trial in Patients with Cancer. J Biol Res Mod.1985;4:264 -272.
21.
Gowen M., Mundy GRActions of Recombinant Interleukin-1, Interleukin-2 and Gamma Interferon on Bone Resorption in Vitro. J Immunol. 1986;136: 2478-2482.
22.
Peterlik M. , Hoffmann O., Swetly P., et al. Recombinant Gamma Interferon Inhibits Prostaglandin Mediated and Parathyroid Hormone Induced Bone Resportion in Cultured Neonatal Mouse Calvaria. Feb Leh1985:287-290, 1985.
23.
Villcek J., Pearlstein KT, Le DS, et al. Interferon Gamma: Interactions with Other Lymphokines. In: The Biology of the Interferon System; (ed) H. Schellekens, 1983.
