FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2247085032> ?p ?o ?g. }

• W2247085032 endingPage "3025" @default.
• W2247085032 startingPage "3025" @default.
• W2247085032 abstract "3025 Background: LBH589A is a novel histone deacetylase inhibitor which inhibits HDAC enzyme activity, activates p21 and inhibits proliferation of tumor cell lines at nanomolar concentrations. Methods: In this phase I trial, LBH589A was administered IV as a 30-minute infusion either on days 1–3 and 8–10 of a 21 day cycle (arm 1) or on days 1–3 and 15–17 of a 28 day cycle (arm 2). Results: Thirteen pts. (median age: 64.3 years; 10M, 3F) have been treated. Tumor types: renal cell (4 pts), NSCLC (2 pts), sarcoma (2 pts), hepatocellular (1 pt), colon (1 pt), others (3 pts). In arm 1, 11 pts. have been treated at dose levels (mg/m2): 1.2 (2 pts), 2.4 (3 pts), 4.8 (3 pts), 7.2 (3 pts). In arm 2, two pts. have been treated at dose levels: 2.4 (1 pt), 4.8 (1 pt). Performance status: 0 (3 pts), 1 (10 pts). One DLT (prolonged G2 thrombocytopenia) has been observed at the 7.2 mg/m2 dose level in arm 1. Other toxicities (all cycles): G3 neutropenia (1 pt), G3 hypoglycemia (1 pt), G2 thrombocytopenia (2 pts), and G2 anemia (2 pts). No abnormalities observed in >100 ECGs. Six of 13 pts. have exhibited stable disease (range 2–8 cycles, tumors: renal (3 pts), sarcoma (1 pt), NSCLC (1 pt), hepatocellular (1 pt)). To determine if LBH589A increases histone acetylation, Western blots were performed on total cell lysates from peripheral blood lymphocytes. Increased acetylation was observed in 1 of 2 pts. at 2.4 mg/m2 and in 2 of 3 pts. at 4.8 mg/m2 up to 24 hrs after the third dose. Onset of acetylation was rapid (1h) and, in 1 patient at 4.8 mg/m2 dose, lasted up to 7 days after the first dose. PK samples were collected on days 1 and 3 of cycle 1 and analyzed using a noncompartmental analysis. Plasma LBH589A concentrations were determined using HPLC/MS/MS assay. AUC increased proportionally with dose and mean AUCs (0–24h) were 37.7, 85.8 and 151.1 ng.h/mL, respectively, for 1.2, 2.4 and 4.8 mg/M2 dose levels on Day 3. Terminal half-life was approximately 15–20 hrs. Conclusions: In this phase I study, LBH589A given IV appears to be well tolerated with consistent PD effects. Additional evaluation is continuing at the 7.2 mg/m2 dose level for arm 1 and at the 9.6 mg/m2 dose level a for arm 2. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis; Novartis Germany Novartis Novartis Novartis" @default.
• W2247085032 created "2016-06-24" @default.
• W2247085032 creator A5010851480 @default.
• W2247085032 creator A5011905014 @default.
• W2247085032 creator A5028833538 @default.
• W2247085032 creator A5029250422 @default.
• W2247085032 creator A5036175709 @default.
• W2247085032 creator A5044120213 @default.
• W2247085032 creator A5058914292 @default.
• W2247085032 creator A5065211401 @default.
• W2247085032 creator A5068014441 @default.
• W2247085032 creator A5084398509 @default.
• W2247085032 date "2004-07-15" @default.
• W2247085032 modified "2023-10-17" @default.
• W2247085032 title "Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of LBH589A: A novel histone deacetylase inhibitor" @default.
• W2247085032 doi "https://doi.org/10.1200/jco.2004.22.90140.3025" @default.
• W2247085032 hasPublicationYear "2004" @default.
• W2247085032 type Work @default.
• W2247085032 sameAs 2247085032 @default.
• W2247085032 citedByCount "6" @default.
• W2247085032 countsByYear W22470850322018 @default.
• W2247085032 crossrefType "journal-article" @default.
• W2247085032 hasAuthorship W2247085032A5010851480 @default.
• W2247085032 hasAuthorship W2247085032A5011905014 @default.
• W2247085032 hasAuthorship W2247085032A5028833538 @default.
• W2247085032 hasAuthorship W2247085032A5029250422 @default.
• W2247085032 hasAuthorship W2247085032A5036175709 @default.
• W2247085032 hasAuthorship W2247085032A5044120213 @default.
• W2247085032 hasAuthorship W2247085032A5058914292 @default.
• W2247085032 hasAuthorship W2247085032A5065211401 @default.
• W2247085032 hasAuthorship W2247085032A5068014441 @default.
• W2247085032 hasAuthorship W2247085032A5084398509 @default.
• W2247085032 hasConcept C104317684 @default.
• W2247085032 hasConcept C111113717 @default.
• W2247085032 hasConcept C112705442 @default.
• W2247085032 hasConcept C126322002 @default.
• W2247085032 hasConcept C185592680 @default.
• W2247085032 hasConcept C2776202225 @default.
• W2247085032 hasConcept C2777063308 @default.
• W2247085032 hasConcept C2778248108 @default.
• W2247085032 hasConcept C2778305200 @default.
• W2247085032 hasConcept C29730261 @default.
• W2247085032 hasConcept C55493867 @default.
• W2247085032 hasConcept C64927066 @default.
• W2247085032 hasConcept C71924100 @default.
• W2247085032 hasConcept C90924648 @default.
• W2247085032 hasConcept C98274493 @default.
• W2247085032 hasConceptScore W2247085032C104317684 @default.
• W2247085032 hasConceptScore W2247085032C111113717 @default.
• W2247085032 hasConceptScore W2247085032C112705442 @default.
• W2247085032 hasConceptScore W2247085032C126322002 @default.
• W2247085032 hasConceptScore W2247085032C185592680 @default.
• W2247085032 hasConceptScore W2247085032C2776202225 @default.
• W2247085032 hasConceptScore W2247085032C2777063308 @default.
• W2247085032 hasConceptScore W2247085032C2778248108 @default.
• W2247085032 hasConceptScore W2247085032C2778305200 @default.
• W2247085032 hasConceptScore W2247085032C29730261 @default.
• W2247085032 hasConceptScore W2247085032C55493867 @default.
• W2247085032 hasConceptScore W2247085032C64927066 @default.
• W2247085032 hasConceptScore W2247085032C71924100 @default.
• W2247085032 hasConceptScore W2247085032C90924648 @default.
• W2247085032 hasConceptScore W2247085032C98274493 @default.
• W2247085032 hasIssue "14_suppl" @default.
• W2247085032 hasLocation W22470850321 @default.
• W2247085032 hasOpenAccess W2247085032 @default.
• W2247085032 hasPrimaryLocation W22470850321 @default.
• W2247085032 hasRelatedWork W1580990163 @default.
• W2247085032 hasRelatedWork W2029175848 @default.
• W2247085032 hasRelatedWork W2030301626 @default.
• W2247085032 hasRelatedWork W2033336929 @default.
• W2247085032 hasRelatedWork W2051615431 @default.
• W2247085032 hasRelatedWork W2074781740 @default.
• W2247085032 hasRelatedWork W2380287092 @default.
• W2247085032 hasRelatedWork W3126958487 @default.
• W2247085032 hasRelatedWork W3151757475 @default.
• W2247085032 hasRelatedWork W4361884305 @default.
• W2247085032 hasVolume "22" @default.
• W2247085032 isParatext "false" @default.
• W2247085032 isRetracted "false" @default.
• W2247085032 magId "2247085032" @default.
• W2247085032 workType "article" @default.