Document Detail


Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS).
MedLine Citation:
PMID:  21538061     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The inhibition of histone deacetylase (HDAC) can induce differentiation, growth arrest, and apoptosis in cancer cells. This phase II multicenter study was undertaken to estimate the efficacy of belinostat, a potent inhibitor of both class I and class II HDAC enzymes, for the treatment of myelodysplastic syndrome (MDS). Adults with MDS and ≤2 prior therapies were treated with belinostat 1,000 mg/m(2) IV on days 1-5 of a 21-day cycle. The primary endpoint was a proportion of confirmed responses during the first 12 weeks of treatment. Responding patients could receive additional cycles until disease progression or unacceptable toxicity. Twenty-one patients were enrolled, and all were evaluable. Patients were a median 13.4 months from diagnosis, and 14 patients (67%) had less than 5% bone marrow blasts. Seventeen patients (81%) were transfusion dependent. Prior therapy included azacytidine (n = 7) and chemotherapy (n = 8). The patients were treated with a median of four cycles (range, 1-8) of belinostat. There was one confirmed response-hematologic improvement in neutrophils-for an overall response rate of 5% (95% CI, 0.2-23). Median overall survival was 17.9 months. Grades 3-4 toxicities considered at least to be possibly related to belinostat were: neutropenia (n = 10), thrombocytopenia (n = 9), anemia (n = 5), fatigue (n = 2), febrile neutropenia (n = 1), headache (n = 1), and QTc prolongation (n = 1). Because the study met the stopping rule in the first stage of enrollment, it was closed to further accrual.
Authors:
Amanda Cashen; Mark Juckett; Alcee Jumonville; Mark Litzow; P J Flynn; John Eckardt; Betsy LaPlant; Kristina Laumann; Charles Erlichman; John DiPersio
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, N.I.H., Extramural     Date:  2011-05-03
Journal Detail:
Title:  Annals of hematology     Volume:  91     ISSN:  1432-0584     ISO Abbreviation:  Ann. Hematol.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-02     Completed Date:  2012-02-23     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9107334     Medline TA:  Ann Hematol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  33-8     Citation Subset:  IM    
Affiliation:
Washington University School of Medicine, St Louis, MO 63110, USA. acashen@dom.wustl.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Disease Progression
Female
Histone Deacetylase Inhibitors / therapeutic use*
Histone Deacetylases / metabolism
Humans
Hydroxamic Acids / therapeutic use*
Male
Middle Aged
Myelodysplastic Syndromes / drug therapy*,  physiopathology
Sulfonamides
Survival Rate
Treatment Outcome
Grant Support
ID/Acronym/Agency:
N01 CM062205/CM/NCI NIH HHS; N01-CM62205/CM/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors; 0/Hydroxamic Acids; 0/Sulfonamides; 0/belinostat; EC 3.5.1.98/Histone Deacetylases
Comments/Corrections

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