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Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer.

Publication ,  Journal Article
Laszlo, J; Huang, AT; Brenckman, WD; Jeffs, C; Koren, H; Cianciolo, G; Metzgar, R; Cashdollar, W; Cox, E; Buckley, CE; Tso, CY; Lucas, VS
Published in: Cancer Res
September 1983

An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broad-scale evaluation of the immune response as a function of interferon dosage. Dose-limiting toxicity was generally due to constitutional symptoms which are remarkably similar to those produced by influenza, although transient peripheral and central neurotoxicity (including deterioration in cognitive and behavioral functions) is observed at higher doses. It is difficult to establish "clean" dose-response effects except for fever and bone marrow suppression, neither of which is a major dose limitation. Enhancement of the immune system was limited to natural killer cells which had a complex dose-response relationship, whereby low interferon concentrations were less stimulatory (than were high doses) following a single dose but gave more sustained stimulation over a 5-week course of 3 times per week i.m. administration. The effects on various measures of monocyte function and of nonspecific immunity (hypersensitivity, immunoglobulins, complement) were negative. We suspect that in practice it may be difficult to exploit the narrow dosage window of immunostimulation, but it is important to note that the nontoxic lower doses were more stimulatory than were the very high doses which are being used in numerous clinical trials.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1983

Volume

43

Issue

9

Start / End Page

4458 / 4466

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Lymphocytes
  • Kinetics
  • Killer Cells, Natural
  • Interferon Type I
  • Humans
  • Hematopoietic Stem Cells
 

Citation

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Laszlo, J., Huang, A. T., Brenckman, W. D., Jeffs, C., Koren, H., Cianciolo, G., … Lucas, V. S. (1983). Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer. Cancer Res, 43(9), 4458–4466.
Laszlo, J., A. T. Huang, W. D. Brenckman, C. Jeffs, H. Koren, G. Cianciolo, R. Metzgar, et al. “Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer.Cancer Res 43, no. 9 (September 1983): 4458–66.
Laszlo J, Huang AT, Brenckman WD, Jeffs C, Koren H, Cianciolo G, et al. Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer. Cancer Res. 1983 Sep;43(9):4458–66.
Laszlo J, Huang AT, Brenckman WD, Jeffs C, Koren H, Cianciolo G, Metzgar R, Cashdollar W, Cox E, Buckley CE, Tso CY, Lucas VS. Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer. Cancer Res. 1983 Sep;43(9):4458–4466.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

September 1983

Volume

43

Issue

9

Start / End Page

4458 / 4466

Location

United States

Related Subject Headings

  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Lymphocytes
  • Kinetics
  • Killer Cells, Natural
  • Interferon Type I
  • Humans
  • Hematopoietic Stem Cells