FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4234568643> ?p ?o ?g. }

• W4234568643 endingPage "3541" @default.
• W4234568643 startingPage "3541" @default.
• W4234568643 abstract "3541 Background: The X-linked inhibitor of apoptosis (XIAP) is a potent anti-apoptotic protein. AEG35156 is a 2nd generation antisense oligonucleotide to human XIAP that enhances cancer cell apoptosis preclinically as a single agent and in combination with chemotherapeutics. Methods: The primary objective was to establish the maximum tolerated dose of AEG35156 given as a 2-hour infusion once weekly following 3 daily loading doses in week 1. Other objectives were to evaluate AEG35156 pharmacokinetics, XIAP inhibition, circulating apoptosis biomarkers and document anti-tumour activity. Results: Twenty-nine adult patients (16 M; 13 F) have been registered. Twenty-three have completed at least one 3-week treatment cycle at doses ranging from 60 to 500mg AEG35156. Treatment has been generally well tolerated, the most common toxicities have been grade I chills/pyrexia, rapidly reversible increases in aPTT at the end of infusion and mild transaminitis. One patient at 240mg had a silent myocardial infarction probably related to prophylactic aspirin withdrawal prior to starting protocol therapy. Three DLTs were observed at AEG35156 350mg: Grade 3 chills/lethargy (mesothelioma), grade 3 transaminitis (colon), transient grade 3 chills/tumour lysis syndrome/transaminitis (small lymphocytic lymphoma). A less intensive dosing protocol was deemed appropriate for future NHL patients and a protocol amendment excluding NHL patients from this study and permitting resumption in patients with solid tumors and including premedication with dexamethasone / acetaminophen was implemented. Dosing at AEG35156 500mg has been completed with no DLTs and the study is ongoing at 650mg. Pharmacokinetics were dose-proportional and linear from 60 to 500mg AEG35156. Mean plasma Cmax at 500mg was 55μg/mL. Decreases in XIAP mRNA have been observed in PBMCs at dose levels ≥240mg and increased levels of circulating biomarkers of apoptosis have been observed in some patients. One patient with NHL who received only a single infusion had rapid clearance of circulating tumour cells and reduction in nodal disease. Conclusions: AEG35156 can be safely delivered by 2-hour infusions and preliminary evidence of XIAP mRNA knockdown and antitumour activity in lymphoma has been observed. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Aegera Therapeutics Inc. Aegera Therapeutics Inc. Aegera Therapeutics Inc. Aegera Therapeutics Inc." @default.
• W4234568643 created "2022-05-12" @default.
• W4234568643 creator A5007325576 @default.
• W4234568643 creator A5023687515 @default.
• W4234568643 creator A5028617609 @default.
• W4234568643 creator A5032939839 @default.
• W4234568643 creator A5039337111 @default.
• W4234568643 creator A5052081777 @default.
• W4234568643 creator A5055792960 @default.
• W4234568643 creator A5067138875 @default.
• W4234568643 date "2008-05-20" @default.
• W4234568643 modified "2023-10-17" @default.
• W4234568643 title "A phase I trial of AEG35156 (XIAP antisense) administered as 2-hour intravenous infusions in patients with advanced tumours" @default.
• W4234568643 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.3541" @default.
• W4234568643 hasPublicationYear "2008" @default.
• W4234568643 type Work @default.
• W4234568643 citedByCount "11" @default.
• W4234568643 countsByYear W42345686432012 @default.
• W4234568643 countsByYear W42345686432016 @default.
• W4234568643 crossrefType "journal-article" @default.
• W4234568643 hasAuthorship W4234568643A5007325576 @default.
• W4234568643 hasAuthorship W4234568643A5023687515 @default.
• W4234568643 hasAuthorship W4234568643A5028617609 @default.
• W4234568643 hasAuthorship W4234568643A5032939839 @default.
• W4234568643 hasAuthorship W4234568643A5039337111 @default.
• W4234568643 hasAuthorship W4234568643A5052081777 @default.
• W4234568643 hasAuthorship W4234568643A5055792960 @default.
• W4234568643 hasAuthorship W4234568643A5067138875 @default.
• W4234568643 hasConcept C112705442 @default.
• W4234568643 hasConcept C126322002 @default.
• W4234568643 hasConcept C185592680 @default.
• W4234568643 hasConcept C190283241 @default.
• W4234568643 hasConcept C22979827 @default.
• W4234568643 hasConcept C2777288759 @default.
• W4234568643 hasConcept C2778594517 @default.
• W4234568643 hasConcept C31573885 @default.
• W4234568643 hasConcept C33195913 @default.
• W4234568643 hasConcept C42219234 @default.
• W4234568643 hasConcept C55493867 @default.
• W4234568643 hasConcept C71924100 @default.
• W4234568643 hasConcept C98274493 @default.
• W4234568643 hasConcept C98424977 @default.
• W4234568643 hasConceptScore W4234568643C112705442 @default.
• W4234568643 hasConceptScore W4234568643C126322002 @default.
• W4234568643 hasConceptScore W4234568643C185592680 @default.
• W4234568643 hasConceptScore W4234568643C190283241 @default.
• W4234568643 hasConceptScore W4234568643C22979827 @default.
• W4234568643 hasConceptScore W4234568643C2777288759 @default.
• W4234568643 hasConceptScore W4234568643C2778594517 @default.
• W4234568643 hasConceptScore W4234568643C31573885 @default.
• W4234568643 hasConceptScore W4234568643C33195913 @default.
• W4234568643 hasConceptScore W4234568643C42219234 @default.
• W4234568643 hasConceptScore W4234568643C55493867 @default.
• W4234568643 hasConceptScore W4234568643C71924100 @default.
• W4234568643 hasConceptScore W4234568643C98274493 @default.
• W4234568643 hasConceptScore W4234568643C98424977 @default.
• W4234568643 hasIssue "15_suppl" @default.
• W4234568643 hasLocation W42345686431 @default.
• W4234568643 hasOpenAccess W4234568643 @default.
• W4234568643 hasPrimaryLocation W42345686431 @default.
• W4234568643 hasRelatedWork W2002127959 @default.
• W4234568643 hasRelatedWork W2004706469 @default.
• W4234568643 hasRelatedWork W2080969318 @default.
• W4234568643 hasRelatedWork W2379280247 @default.
• W4234568643 hasRelatedWork W2604484584 @default.
• W4234568643 hasRelatedWork W2899072855 @default.
• W4234568643 hasRelatedWork W2942467058 @default.
• W4234568643 hasRelatedWork W2972898444 @default.
• W4234568643 hasRelatedWork W3151787567 @default.
• W4234568643 hasRelatedWork W3185247380 @default.
• W4234568643 hasVolume "26" @default.
• W4234568643 isParatext "false" @default.
• W4234568643 isRetracted "false" @default.
• W4234568643 workType "article" @default.