Phase I trials of poly(I, C) complexes in advanced cancer Journal Article
| Authors: | Krown, S. E.; Kerr, D.; Stewart, W. E. 2nd; Field, A. K.; Oettgen, H. F. |
| Article Title: | Phase I trials of poly(I, C) complexes in advanced cancer |
| Abstract: | We have performed Phase I trials of two synthetic double-stranded polyribonucleotide complexes—poly(I, C)-LC, a complex of polyinosinic-polycytidylic acid with poly-L-lysine and carboxymethylcellulose, and poly(I, C)-L, which lacks carboxymethylcellulose—in patients with advanced cancer. With poly(I, C)-LC, several treatment schedules were investigated in an attempt to decrease toxicity and maximize interferon (IFN) induction. The best tolerated was an alternate-day schedule, with gradual dose escalation. Daily short infusions and continuous (24-h) infusions were tolerated less well. Maximum tolerated doses varied over a several hundredfold dose range. Toxicity consisted of fever, rigors, hypotension, and blood count depression. Two patients treated with poly(I, C)-L developed systemic allergic reactions, and antibodies to poly(I, C)-L and its components were detected in the serum of some patients treated with both compounds. IFN-α was induced in most patients at serum levels similar to those achieved after intramuscular administration of human IFN-α. Of 32 patients, one with renal cell carcinoma showed partial tumor regression. Poly(I, C) complexes are effective IFN inducers in humans, but their toxicity limits their use in cancer patients. © 1985 Raven Press, New York. |
| Keywords: | adult; cancer chemotherapy; clinical article; aged; middle aged; unclassified drug; drowsiness; diarrhea; drug efficacy; neurotoxicity; anorexia; neoplasms; liver toxicity; lung toxicity; leukopenia; nausea; thrombocytopenia; myalgia; kidney neoplasms; chill; drug hypersensitivity; fever; flushing; confusion; gastrointestinal toxicity; hypotension; psychological aspect; kidney; immunotherapy; carcinoma, renal cell; cardiovascular system; killer cells, natural; polyinosinic polycytidylic acid; carboxymethylcellulose polycytidylic polyinosinic acid polylysine; carboxymethylcellulose; interferon inducers; poly i-c; polylysine; headache; drug dose; phase 1 clinical trial; kidney cancer; drug therapy; drug tolerance; heart; adverse drug reaction; therapy; tachycardia; antibody formation; intravenous drug administration; bronchospasm; nervous system; vertigo; drug evaluation; intoxication; respiratory system; thirst; interferons; humans; human; male; female; article; methylcellulose; drug antibody; blood and hemopoietic system; peripheral vascular system; poly(inosinic acid cytidylic acid lysine); poly(i, c)-l; poly(i, c)-lc; polyribonucleotide; acrocyanosis |
| Journal Title: | Journal of Biological Response Modifiers |
| Volume: | 4 |
| Issue: | 6 |
| ISSN: | 0732-6580 |
| Publisher: | Lippincott-Raven |
| Date Published: | 1985-12-01 |
| Start Page: | 640 |
| End Page: | 649 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 2418162 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 26 October 2021 -- Source: Scopus |
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