Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/10904
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dc.contributor.authorHerbertson, Rebecca Aen
dc.contributor.authorTebbutt, Niall Cen
dc.contributor.authorLee, Fook-Theanen
dc.contributor.authorMacFarlane, David Jen
dc.contributor.authorChappell, Bridgeten
dc.contributor.authorMicallef, Noelen
dc.contributor.authorLee, Sze-Tingen
dc.contributor.authorSaunder, Timothyen
dc.contributor.authorHopkins, Wendieen
dc.contributor.authorSmyth, Fiona Een
dc.contributor.authorWyld, David Ken
dc.contributor.authorBellen, Johnen
dc.contributor.authorSonnichsen, Daryl Sen
dc.contributor.authorBrechbiel, Martin Wen
dc.contributor.authorMurone, Carmelen
dc.contributor.authorScott, Andrew Men
dc.date.accessioned2015-05-16T00:28:53Z
dc.date.available2015-05-16T00:28:53Z
dc.date.issued2009-10-13en
dc.identifier.citationClinical Cancer Research 2009; 15(21): 6709-15en
dc.identifier.govdoc19825951en
dc.identifier.otherPUBMEDen
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/10904en
dc.description.abstractThis phase I study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 [a humanized anti-Lewis Y (Le(y)) antibody conjugated with calicheamicin in patients with advanced cancers expressing the Le(y) antigen.The primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. Secondary objectives included response rates and change in tumor metabolism. Patients with progressive, measurable, and Le(y) positive malignancies were eligible for enrollment in one of two dose cohorts, 1.0 and 2.6 mg/m(2). The first cycle was trace labeled with (111)In for biodistribution assessment using gamma camera imaging. Subsequent cycles were administered every 3 weeks up to a maximum of six cycles, depending on toxicity and response. Pharmacokinetic analysis was based on radioassay and ELISA.Nine patients were enrolled in the study. Biodistribution images showed initial blood pool activity, followed by markedly increased hepatic uptake by day 2, and fast blood clearance in all patients. There was low uptake in tumor in all patients. The overall T(1/2)beta of (111)In-CMD-193 was 102.88 +/- 35.67 hours, with no statistically significant difference between the two dose levels. One patient had a partial metabolic response on (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG PET) after four cycles, but no radiological responses were observed. Myelosuppression and effects on liver function were the most significant adverse effects.CMD-193 shows rapid blood clearance and increased hepatic uptake compared with prior studies of the parental antibody hu3S193. These results highlight the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics to assist in clinical development.en
dc.language.isoenen
dc.subject.otherAgeden
dc.subject.otherAntibodies, Monoclonal.therapeutic useen
dc.subject.otherAntibodies, Monoclonal, Humanizeden
dc.subject.otherAntineoplastic Agents.pharmacokineticsen
dc.subject.otherFemaleen
dc.subject.otherHumansen
dc.subject.otherImmunoconjugates.administration & dosage.adverse effects.metabolism.pharmacokineticsen
dc.subject.otherLewis Blood-Group System.immunologyen
dc.subject.otherMaleen
dc.subject.otherMiddle Ageden
dc.subject.otherNeoplasms, Glandular and Epithelial.drug therapyen
dc.titlePhase I biodistribution and pharmacokinetic study of Lewis Y-targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers.en
dc.typeJournal Articleen
dc.identifier.journaltitleClinical Cancer Researchen
dc.identifier.affiliationLudwig Institute for Cancer Research, Austin Hospital, Melbourne, Australiaen
dc.identifier.doi10.1158/1078-0432.CCR-09-0536en
dc.description.pages6709-15en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/19825951en
dc.type.austinJournal Articleen
local.name.researcherMurone, Carmel
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.languageiso639-1en-
crisitem.author.deptMedical Oncology-
crisitem.author.deptOlivia Newton-John Cancer Wellness and Research Centre-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
crisitem.author.deptMolecular Imaging and Therapy-
crisitem.author.deptOlivia Newton-John Cancer Research Institute-
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