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Phase I Study of Pharmacological and Immunological Effects of Human Lymphoblastoid Interferon Given to Patients with Cancer¹

Departments of Medicine [J. L., A. T. H., W. D. B., C. J., G. C., E. C., C. E. B., C. Y. T., V. S. L.] and Microbiology-Immunology [H. K., R. M., W. C.], Duke University Medical Center, Durham, North Carolina 27710

An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broadscale 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.

¹ Supported by Contract CM-07343-22 and Grants CA 11265-13 and CA 14236 from the Department of Health Services, National Cancer Institute. Presented in part at the 73rd meeting of the American Association for Cancer Research, St. Louis, Mo., April 1982 (21).

² To whom requests for reprints should be addressed, at Box 3835, Duke Medical Center, Durham, N. C. 27710.

Received 3/17/83. Accepted 6/10/83.