FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2586949235> ?p ?o ?g. }

• W2586949235 abstract "Abstract Background: Serotonin (5-HT) is a lymphocyte growth factor, and lymphocytes bear 5-HT receptors. Fz has anti-serotonergic properties and a favorable safety profile. Fz inhibits growth of Jurkat leukemia cells at concentrations of 1–10 μM (Schleuning M et al, Anticancer Research 1993;13:599–602). Other serotonin receptor antagonists have been shown to have in vitro and pre-clinical in vivo anti-myeloma effects mainly mediated by apoptosis (Ocio EM, et al, Blood 2006 108:Abs 2597). In vitro studies show 10μM Fz exposure for 18hr kills many myeloma and leukemic cell lines, while sparing non-activated, normal, human lymphocytes. In rat studies, Fz partitions into bone marrow (BM) 100× more avidly than into blood. Fz was thus selected for a proof of concept phase 1 trial in patients (pts) with previously treated myeloma. Methods: Pts with myeloma had failed at least 2 prior regimens; had measurable serum or urine M-proteins, or skewed free light chain ratio per central lab assay; had adequate organ function and performance status (ECOG &lt;3); and were not on selective serotoin reuptake inhibitors (SSRIs), tricyclic, or norepinephrine reuptake inhibitor drugs or other anti-serotonergic agents. Fz was given i.v. in a dose escalating “3+3 design” in three divided 5-minute injections at 0, 6, and 12 hrs once every 28 days. Total Fz doses per 3-bolus exposure were 0.11, 0.23, 0.34, 0.57, 0.80, and 1.14 mg/kg. Serum samples for Fz PK analysis were collected from all patients during cycle 1. A single (time-paired with a serum PK sample) BM biopsy for BM Fz level was obtained from a subset of pts. Results: 21 pts (13M; 8F) from 7 sites in the U.S. and India, median age 55 yrs (range 30–75) were enrolled, 3 pts were enrolled per dose cohort, except for 6 pts at 0.34 mg/kg. Median number prior regimens was 4; 15/21 had prior thalidomide or lenalidomide or both; 10/21 had prior bortezomib; 8/21 had prior stem cell transplant (including 2 with tandem transplant, 1 had a third salvage transplant). A MTD was not reached. One DLT, grade 3 extra-pyramidal reaction (EPR) of acute dystonia with stiff jaw, occurred at 0.34 mg/kg. Six pts experienced EPR (4M; 2F) typically occurring 30–36 hrs post first dose; intensity and frequency were not dose related. All EPR except the 1 DLT were grade 1 or 2. Fifteen serious adverse events (SAEs) occurred in 10 pts, all assessed as unrelated to Fz. The most common ≥ gr 3 non-serious AEs were anemia, thrombocytopenia, and back pain, none of which was assessed as related to Fz. All cases of orthostatic hypotension, agitation, EPR, sedation, somnolence, and 3 of 4 cases of fatigue were deemed related to Fz. Comparison of time-paired BM and serum Fz concentrations in 6 pts showed 4–77-fold higher Fz levels in the marrow over serum in the first 49 hrs post-dosing. The best response through 2 cycles of treatment per Blade criteria in 19 evaluable pts was stable disease in 3 pts (0.23, 0.34, and 0.80 mg/kg; duration 2, 5, and 6 cycles). Conclusion: Fluphenazine may be safely given to pts with relapsed and refractory myeloma at the doses and schedule described, with EPR and sedation that are generally mild and manageable. Fz partitions 1–2 log greater into human BM compared with serum. A MTD was not reached, and additional studies are planned with more dose-intensive schedules." @default.
• W2586949235 created "2017-02-17" @default.
• W2586949235 creator A5017657024 @default.
• W2586949235 creator A5023752321 @default.
• W2586949235 creator A5029801761 @default.
• W2586949235 creator A5041561013 @default.
• W2586949235 creator A5044841069 @default.
• W2586949235 creator A5044878283 @default.
• W2586949235 creator A5059184446 @default.
• W2586949235 creator A5059799734 @default.
• W2586949235 creator A5069728018 @default.
• W2586949235 creator A5069926553 @default.
• W2586949235 creator A5071770976 @default.
• W2586949235 creator A5073978900 @default.
• W2586949235 creator A5030339254 @default.
• W2586949235 date "2008-11-16" @default.
• W2586949235 modified "2023-09-30" @default.
• W2586949235 title "A Phase 1 Trial of Fluphenazine HCl (Fz), a Serotonin Antagonist, in Relapsed and Refractory Multiple Myeloma" @default.
• W2586949235 doi "https://doi.org/10.1182/blood.v112.11.5188.5188" @default.
• W2586949235 hasPublicationYear "2008" @default.
• W2586949235 type Work @default.
• W2586949235 sameAs 2586949235 @default.
• W2586949235 citedByCount "1" @default.
• W2586949235 countsByYear W25869492352020 @default.
• W2586949235 crossrefType "journal-article" @default.
• W2586949235 hasAuthorship W2586949235A5017657024 @default.
• W2586949235 hasAuthorship W2586949235A5023752321 @default.
• W2586949235 hasAuthorship W2586949235A5029801761 @default.
• W2586949235 hasAuthorship W2586949235A5030339254 @default.
• W2586949235 hasAuthorship W2586949235A5041561013 @default.
• W2586949235 hasAuthorship W2586949235A5044841069 @default.
• W2586949235 hasAuthorship W2586949235A5044878283 @default.
• W2586949235 hasAuthorship W2586949235A5059184446 @default.
• W2586949235 hasAuthorship W2586949235A5059799734 @default.
• W2586949235 hasAuthorship W2586949235A5069728018 @default.
• W2586949235 hasAuthorship W2586949235A5069926553 @default.
• W2586949235 hasAuthorship W2586949235A5071770976 @default.
• W2586949235 hasAuthorship W2586949235A5073978900 @default.
• W2586949235 hasConcept C126322002 @default.
• W2586949235 hasConcept C143998085 @default.
• W2586949235 hasConcept C2776063141 @default.
• W2586949235 hasConcept C2776364478 @default.
• W2586949235 hasConcept C2779609412 @default.
• W2586949235 hasConcept C2911091166 @default.
• W2586949235 hasConcept C71924100 @default.
• W2586949235 hasConcept C90924648 @default.
• W2586949235 hasConcept C98274493 @default.
• W2586949235 hasConceptScore W2586949235C126322002 @default.
• W2586949235 hasConceptScore W2586949235C143998085 @default.
• W2586949235 hasConceptScore W2586949235C2776063141 @default.
• W2586949235 hasConceptScore W2586949235C2776364478 @default.
• W2586949235 hasConceptScore W2586949235C2779609412 @default.
• W2586949235 hasConceptScore W2586949235C2911091166 @default.
• W2586949235 hasConceptScore W2586949235C71924100 @default.
• W2586949235 hasConceptScore W2586949235C90924648 @default.
• W2586949235 hasConceptScore W2586949235C98274493 @default.
• W2586949235 hasLocation W25869492351 @default.
• W2586949235 hasOpenAccess W2586949235 @default.
• W2586949235 hasPrimaryLocation W25869492351 @default.
• W2586949235 hasRelatedWork W1199719327 @default.
• W2586949235 hasRelatedWork W2531097482 @default.
• W2586949235 hasRelatedWork W2532111429 @default.
• W2586949235 hasRelatedWork W2550582210 @default.
• W2586949235 hasRelatedWork W2550696733 @default.
• W2586949235 hasRelatedWork W2555141054 @default.
• W2586949235 hasRelatedWork W2560353175 @default.
• W2586949235 hasRelatedWork W2562731214 @default.
• W2586949235 hasRelatedWork W2563131420 @default.
• W2586949235 hasRelatedWork W2587498788 @default.
• W2586949235 hasRelatedWork W2588092501 @default.
• W2586949235 hasRelatedWork W2589000975 @default.
• W2586949235 hasRelatedWork W2594371296 @default.
• W2586949235 hasRelatedWork W2614035684 @default.
• W2586949235 hasRelatedWork W2736149368 @default.
• W2586949235 hasRelatedWork W2991241273 @default.
• W2586949235 hasRelatedWork W2993774309 @default.
• W2586949235 hasRelatedWork W3096297243 @default.
• W2586949235 hasRelatedWork W3212884449 @default.
• W2586949235 hasRelatedWork W961290459 @default.
• W2586949235 isParatext "false" @default.
• W2586949235 isRetracted "false" @default.
• W2586949235 magId "2586949235" @default.
• W2586949235 workType "article" @default.