Matches in SemOpenAlex for { <https://semopenalex.org/work/W2247188379> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W2247188379 endingPage "8548" @default.
- W2247188379 startingPage "8548" @default.
- W2247188379 abstract "8548 Vorinostat, a histone deacetylase inhibitor, affects cell growth by modifying the transcription of cellular proteins (histones, transcription factors, ubiqutin E3 ligases and stress response proteins). In vitro, vorinostat showed synergistic cytotoxicity with proteasome inhibitors in MM cells by disruption of aggresome function and induction of ER stress (Pei, 2004). The study aims were to determine the MTD, pharmacokinetics (PK) and pharmacodynamics (PD) of vorinostat plus Bort in MM pts. Twenty-three pts were treated. Median age was 54 yrs (range 39–78). Median time from MM diagnosis to study entry was 5.3 yrs (range 1.5–9). Isotypes were IgG (n=11), IgA (n=4), light chain (n=8). Fourteen pts had complex karyotypes. Median number of prior regimens was 7 (range 3–13), including autologous transplant (n=20), thalidomide (n=23) and lenalidomide (n=17). Nineteen pts had a median of 2 (range: 1–5) Bort-based prior regimens (table below). Median time from last therapy to study was 20 days (range 15–39). Pts recieved Bort 1.3 mg/ m2 IV days 1, 4, 8 and 11 and vorinostat 100–400 mg days 4–11. Five 3- pt cohorts were evaluated at each level. Two pts in the 500 mg level had DLTs: prolonged QT and fatigue. Additional 8 pts were treated at MTD. Grade 3–4 toxicities included myelosuppression requiring transfusion (n= 13) and growth factors (n=6), fatigue (n=11), diarrhea (n=5), atrial fibrillation (n=1), shingles (n=1) and pneumonia (n=2). In 21 pts evaluable for response after cycle 2, there were 2 VGPR and 7 PR (ORR of 42%), 10 pts had SD and 2 had PD. The PK of vorinostat after a single oral dose were linear from 100–500 mg with mean AUC of 0.7 + 0.45 to 4.4+ 0.07 mM/h, Cmax 0.3 + 0.14 to 1.2 + 0.06 mM and Tmax 1.3 + 0.4 to 2.3 + 2.5 /h. Ten pts had CD138+ cells isolated from bone marrow on day 1 and on day 11 of cycle 1; PD studies showed reduction of NF-KB, Bcl-2, bcl-xl, p21, XIAP in responders compared to pts with SD/PD. MTD is Bort 1.3 mg/ m2 d 1, 4, 8, 11 and vorinostat 400 mg days 4–11. The regimen is well tolerated and has promising activity in MM. Prior Bortezomib No of Pts Response VGPR PR SD PD NE Naïve 4 1 2 1 Prior treatment 10 1 2 5 1 1 Refractory 9 3 4 1 1 PR, partial response; VGPR very good PR; SD, stable disease; PD progressive disease; NE not evaluable; prior treatment indicate initial response followed by progression; refractory indicate pts who never responsed to Bort. No significant financial relationships to disclose." @default.
- W2247188379 created "2016-06-24" @default.
- W2247188379 creator A5006790110 @default.
- W2247188379 creator A5012068082 @default.
- W2247188379 creator A5037249059 @default.
- W2247188379 creator A5044889942 @default.
- W2247188379 creator A5048605850 @default.
- W2247188379 creator A5049910941 @default.
- W2247188379 creator A5052340302 @default.
- W2247188379 creator A5054301787 @default.
- W2247188379 creator A5055751549 @default.
- W2247188379 creator A5062978212 @default.
- W2247188379 creator A5074097873 @default.
- W2247188379 date "2008-05-20" @default.
- W2247188379 modified "2023-09-27" @default.
- W2247188379 title "Phase I trial of vorinostat plus bortezomib (bort) in relapsed/refractory multiple myeloma (mm) patients (pts)" @default.
- W2247188379 doi "https://doi.org/10.1200/jco.2008.26.15_suppl.8548" @default.
- W2247188379 hasPublicationYear "2008" @default.
- W2247188379 type Work @default.
- W2247188379 sameAs 2247188379 @default.
- W2247188379 citedByCount "13" @default.
- W2247188379 crossrefType "journal-article" @default.
- W2247188379 hasAuthorship W2247188379A5006790110 @default.
- W2247188379 hasAuthorship W2247188379A5012068082 @default.
- W2247188379 hasAuthorship W2247188379A5037249059 @default.
- W2247188379 hasAuthorship W2247188379A5044889942 @default.
- W2247188379 hasAuthorship W2247188379A5048605850 @default.
- W2247188379 hasAuthorship W2247188379A5049910941 @default.
- W2247188379 hasAuthorship W2247188379A5052340302 @default.
- W2247188379 hasAuthorship W2247188379A5054301787 @default.
- W2247188379 hasAuthorship W2247188379A5055751549 @default.
- W2247188379 hasAuthorship W2247188379A5062978212 @default.
- W2247188379 hasAuthorship W2247188379A5074097873 @default.
- W2247188379 hasConcept C104317684 @default.
- W2247188379 hasConcept C121332964 @default.
- W2247188379 hasConcept C126322002 @default.
- W2247188379 hasConcept C142424586 @default.
- W2247188379 hasConcept C143998085 @default.
- W2247188379 hasConcept C185592680 @default.
- W2247188379 hasConcept C2776063141 @default.
- W2247188379 hasConcept C2776262904 @default.
- W2247188379 hasConcept C2776364478 @default.
- W2247188379 hasConcept C2777478702 @default.
- W2247188379 hasConcept C2778305200 @default.
- W2247188379 hasConcept C55493867 @default.
- W2247188379 hasConcept C64927066 @default.
- W2247188379 hasConcept C71924100 @default.
- W2247188379 hasConcept C87355193 @default.
- W2247188379 hasConceptScore W2247188379C104317684 @default.
- W2247188379 hasConceptScore W2247188379C121332964 @default.
- W2247188379 hasConceptScore W2247188379C126322002 @default.
- W2247188379 hasConceptScore W2247188379C142424586 @default.
- W2247188379 hasConceptScore W2247188379C143998085 @default.
- W2247188379 hasConceptScore W2247188379C185592680 @default.
- W2247188379 hasConceptScore W2247188379C2776063141 @default.
- W2247188379 hasConceptScore W2247188379C2776262904 @default.
- W2247188379 hasConceptScore W2247188379C2776364478 @default.
- W2247188379 hasConceptScore W2247188379C2777478702 @default.
- W2247188379 hasConceptScore W2247188379C2778305200 @default.
- W2247188379 hasConceptScore W2247188379C55493867 @default.
- W2247188379 hasConceptScore W2247188379C64927066 @default.
- W2247188379 hasConceptScore W2247188379C71924100 @default.
- W2247188379 hasConceptScore W2247188379C87355193 @default.
- W2247188379 hasIssue "15_suppl" @default.
- W2247188379 hasLocation W22471883791 @default.
- W2247188379 hasOpenAccess W2247188379 @default.
- W2247188379 hasPrimaryLocation W22471883791 @default.
- W2247188379 hasRelatedWork W1967018540 @default.
- W2247188379 hasRelatedWork W1976298557 @default.
- W2247188379 hasRelatedWork W1977454730 @default.
- W2247188379 hasRelatedWork W2006866162 @default.
- W2247188379 hasRelatedWork W2066264051 @default.
- W2247188379 hasRelatedWork W2070433411 @default.
- W2247188379 hasRelatedWork W2071115015 @default.
- W2247188379 hasRelatedWork W2110957729 @default.
- W2247188379 hasRelatedWork W2118335184 @default.
- W2247188379 hasRelatedWork W2129890171 @default.
- W2247188379 hasRelatedWork W2130696468 @default.
- W2247188379 hasRelatedWork W2131612416 @default.
- W2247188379 hasRelatedWork W2135619784 @default.
- W2247188379 hasRelatedWork W2141920998 @default.
- W2247188379 hasRelatedWork W2142629029 @default.
- W2247188379 hasRelatedWork W2149386327 @default.
- W2247188379 hasRelatedWork W2169409181 @default.
- W2247188379 hasRelatedWork W2499859474 @default.
- W2247188379 hasRelatedWork W2558178039 @default.
- W2247188379 hasRelatedWork W3108090032 @default.
- W2247188379 hasVolume "26" @default.
- W2247188379 isParatext "false" @default.
- W2247188379 isRetracted "false" @default.
- W2247188379 magId "2247188379" @default.
- W2247188379 workType "article" @default.