Phase I trial of recombinant interferon gamma by 1-hour IV infusion Journal Article
| Authors: | Vadhan-Raj, S.; Nathan, C. F.; Sherwin, S. A.; Oettgen, H. F.; Krown, S. E. |
| Article Title: | Phase I trial of recombinant interferon gamma by 1-hour IV infusion |
| Abstract: | Fifteen patients with advanced malignancy were treated with recombinant interferon gamma (rIFN-γ) (specific activity ~2 x 107 units/mg, purity >99%) given by 1-hour iv infusion three times a week for 6 weeks, at fixed dose levels of 0.1, 0.5, 1.0, or 2.0 mg/m2/day. The common side effects were constitutional symptoms, including fever, chills, myalgias, and headache, but these were less severe than those observed following daily 6-hour iv infusions. Significant changes in blood cell counts and routine serum chemistries were not observed, but there was a dose-dependent increase in serum triglyceride levels. The maximum safely tolerated dose achieved was 1.0 mg/m2/day. Peak serum interferon levels occurred at the midpoint of the infusion and were dose-dependent. rIFN-γ was rapidly cleared from serum and no detectable activity was found 2 hours after the infusion. Two patients, both with B-cell malignancies, showed objective evidence of tumor regression during the treatment. Treatment was associated with an increase in serum levels of β2-microglobulin and the H2O2 secretory capacity of peripheral blood monocytes. We conclude that rIFN-γ administered by short iv infusion can induce biological activities and causes less toxicity than when given by prolonged iv infusion. |
| Keywords: | adult; cancer chemotherapy; clinical article; aged; middle aged; leukemia; lymphatic metastasis; anorexia; neoplasms; melanoma; nausea; vomiting; myalgia; orthostatic hypotension; dose-response relationship, drug; b lymphocyte; chill; fever; gastrointestinal toxicity; kinetics; gamma interferon; recombinant gamma interferon; paracetamol; cardiovascular system; lymphoma; headache; kaposi sarcoma; blood cell count; drug blood level; phase 1 clinical trial; monocytes; drug therapy; toxicity; adverse drug reaction; therapy; hypertriglyceridemia; clinical trials; infusions, parenteral; intravenous drug administration; triglycerides; endocrine system; recombinant; thyroid medullary carcinoma; vertigo; drug evaluation; intoxication; interferon type ii; dna, recombinant; cancer; humans; human; male; female; priority journal; beta 2-microglobulin; lipoproteins, vldl; beta 2 microglobulin blood level |
| Journal Title: | Cancer Treatment Reports |
| Volume: | 70 |
| Issue: | 5 |
| ISSN: | 0361-5960 |
| Publisher: | National Cancer Institute |
| Date Published: | 1986-05-01 |
| Start Page: | 609 |
| End Page: | 614 |
| Language: | English |
| PUBMED: | 3085930 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 18 August 2021 -- Source: Scopus; Acknowledgments: We thank Dr. Ayad Al-Katib for performing lymphocyte surface marker studies, Dr. Ravi Bhalla for performing β2-microglobulin determinations, Mary Agnes Templeton for assistance in data collection and analysis, and Catherine Cassidy for preparation of the manuscript. |
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