A Dose-Escalation Study of Recombinant Human Interleukin-18 Using Two Different Schedules of Administration in Patients with Cancer
dc.contributor.author | Robertson, Michael J. | |
dc.contributor.author | Kirkwood, John M. | |
dc.contributor.author | Logan, Theodore F. | |
dc.contributor.author | Koch, Kevin M. | |
dc.contributor.author | Kathman, Steven | |
dc.contributor.author | Kirby, Lyndon C. | |
dc.contributor.author | Bell, William N. | |
dc.contributor.author | Thurmond, Linda M. | |
dc.contributor.author | Weisenbach, Jill | |
dc.contributor.author | Dar, Mohammed M. | |
dc.contributor.department | Medicine, School of Medicine | en_US |
dc.date.accessioned | 2023-03-27T15:57:38Z | |
dc.date.available | 2023-03-27T15:57:38Z | |
dc.date.issued | 2008-06 | |
dc.description.abstract | Purpose: Interleukin-18 (IL-18) is an immunostimulatory cytokine with antitumor activity in preclinical models. A phase I study of recombinant human IL-18 (rhIL-18) was done to determine the toxicity, pharmacokinetics, and biological activities of rhIL-18 administered at different doses in two different schedules to patients with advanced cancer. Experimental design: Cohorts of three to four patients were given escalating doses of rhIL-18 as a 2-h i.v. infusion either on 5 consecutive days repeated every 28 days (group A) or once a week (group B) for up to 6 months. Toxicities were graded using standard criteria. Blood samples were obtained for safety, pharmacokinetic, and pharmacodynamic measurements. Results: Nineteen patients (10 melanoma and 9 renal cell cancer) were given rhIL-18 in doses of 100, 500, or 1,000 microg/kg (group A) or 100, 1,000, or 2,000 microg/kg (group B). Common side effects included chills, fever, headache, fatigue, and nausea. Common laboratory abnormalities included transient, asymptomatic grade 1 to 3 lymphopenia, grade 1 to 4 hyperglycemia, grade 1 to 2 anemia, neutropenia, hypoalbuminemia, liver enzyme elevations, and serum creatinine elevations. No dose-limiting toxicities were observed. Biological effects of rhIL-18 included transient lymphopenia and increased expression of activation antigens on lymphocytes. Increases in serum concentrations of IFN-gamma, granulocyte macrophage colony-stimulating factor, and IL-18-binding protein were observed following dosing. Conclusions: rhIL-18 can be given in biologically active doses by either weekly infusions or daily infusions for 5 days repeated every 28 days to patients with advanced cancer. Toxicity was generally mild to moderate, and a maximum tolerated dose of rhIL-18 by either schedule was not determined. | en_US |
dc.eprint.version | Author's manuscript | en_US |
dc.identifier.citation | Robertson MJ, Kirkwood JM, Logan TF, et al. A dose-escalation study of recombinant human interleukin-18 using two different schedules of administration in patients with cancer. Clin Cancer Res. 2008;14(11):3462-3469. doi:10.1158/1078-0432.CCR-07-4740 | en_US |
dc.identifier.uri | https://hdl.handle.net/1805/32078 | |
dc.language.iso | en_US | en_US |
dc.publisher | American Association for Cancer Research | en_US |
dc.relation.isversionof | 10.1158/1078-0432.CCR-07-4740 | en_US |
dc.relation.journal | Clinical Cancer Research | en_US |
dc.rights | Publisher Policy | en_US |
dc.source | PMC | en_US |
dc.subject | Antineoplastic agents | en_US |
dc.subject | Interleukin-18 | en_US |
dc.subject | Neoplasms | en_US |
dc.subject | Recombinant proteins | en_US |
dc.subject | Maximum tolerated dose | en_US |
dc.title | A Dose-Escalation Study of Recombinant Human Interleukin-18 Using Two Different Schedules of Administration in Patients with Cancer | en_US |
dc.type | Article | en_US |