| A phase I clinical trial of recombinant DNA gamma interferon. | |
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MedLine Citation:
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PMID: 3106584 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recombinant gamma interferon (r-GIFN) demonstrates in vitro and in vivo characteristics that contrast with those of alpha and beta interferons. It has relatively weak antiviral properties, yet relatively potent immunomodulatory effects. A phase I trial was performed with r-GIFN (specific activity 2.6 X 10(6) IU/mg protein), administered as a continuous intravenous (IV) infusion over 24 hours for five days (Cl X 5) and repeated every 28 days. This schedule was chosen based on the short half-life of r-GIFN in animal systems and the in vitro augmentation of biologic effects with continuous exposure to interferons. Twenty-one patients with refractory solid tumors received 46 evaluable courses of therapy. The dose-limiting toxicities included fever, flu-like symptoms, cardiovascular toxicity, and neurotoxicity. The cardiovascular toxicity included hypotension and one episode of cardiac ischemia with chest pain. Neurotoxicity consisted of lethargy and confusion. These toxicities were reversible, and although dose-limiting, occurred sporadically throughout all dosage levels. Mild to moderately severe non-dose-limiting toxicities included nausea and vomiting, leukopenia, and liver function abnormalities. Other infrequent toxicities included hypocalcemia, diarrhea, constipation, and alopecia. The maximally tolerated dose of r-GIFN on this schedule is 0.5 X 10(6) IU/m2/d. Partial responses were seen in one patient with metastatic melanoma and in one patient with renal cell carcinoma. Toxicity and antitumor activity were seen at doses where interferon serum levels could not be detected by radioimmunoassay. In addition, the toxicity and antitumor activity seen were at much lower doses than previously described for shorter infusion schedules of other recombinant gamma interferon preparations. Differences in biologic activity of interferon preparations and/or differences in scheduling may account for this variability. Although this study defines a recommended phase II dose of r-GIFN based on the maximally tolerated dose, the optimal therapeutic index may exist at a lower dosage level. |
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Authors:
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T D Brown; J Koeller; K Beougher; J Golando; E M Bonnem; R J Spiegel; D D Von Hoff |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of clinical oncology : official journal of the American Society of Clinical Oncology Volume: 5 ISSN: 0732-183X ISO Abbreviation: J. Clin. Oncol. Publication Date: 1987 May |
Date Detail:
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Created Date: 1987-06-19 Completed Date: 1987-06-19 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8309333 Medline TA: J Clin Oncol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 790-8 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Confusion / chemically induced Drug Evaluation Female Fever / etiology Heart / drug effects Humans Interferon-gamma / administration & dosage, adverse effects, therapeutic use* Leukopenia / chemically induced Male Middle Aged Nausea / chemically induced Neoplasms / drug therapy* Recombinant Proteins / therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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RR01346/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Recombinant Proteins; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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