Various recombinant and nonrecombinant Alpha and Gamma interferons have been tested in Phase I trials in cancer patients in order to study the toxicity, antitumor effects, immunomodulatory effects and pharmacokinetics of these preparations. The initial Phase I trials employed highly purified recombinant leukocyte A interferon and human Namalva cell lymphoblastoid interferon and have been previously reported. We have recently completed 3 Phase I studies with recombinant and nonrecombinant Gamma interferons. Toxicity for each of these preparations was similar to Alpha interferons, with a flu-like syndrome as well as minor hematologic toxicity, primarily decreased circulatory leukocytes. Dose-dependent serum levels of IFN were detected, using both a biologic assay and enzyme-linked immunosorbent assay for the recombinant Gamma interferon. No antitumor responses were seen. We are also completing a phase I trial with recombinant leukocyte interferon to determine the optimal immunomodulating dose. Doses studied range from one thousand to one million units injected daily or biweekly. We have also begun a phase I trial to determine the optimal ummunomodulatory dose with recombinant interferon-Gamma in patients with melanoma without metastasis but a high liklihood of recurrent disease.
