Annals of Hematology

, Volume 91, Issue 1, pp 33–38

Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS)

  • Amanda Cashen
  • Mark Juckett
  • Alcee Jumonville
  • Mark Litzow
  • P. J. Flynn
  • John Eckardt
  • Betsy LaPlant
  • Kristina Laumann
  • Charles Erlichman
  • John DiPersio
Original Article


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/m2 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.


Belinostat PXD101 Myelodysplastic syndrome Histone deacetylase inhibitor 


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Amanda Cashen
    • 1
  • Mark Juckett
    • 2
  • Alcee Jumonville
    • 3
  • Mark Litzow
    • 4
  • P. J. Flynn
    • 5
  • John Eckardt
    • 6
  • Betsy LaPlant
    • 7
  • Kristina Laumann
    • 7
  • Charles Erlichman
    • 7
  • John DiPersio
    • 1
  1. 1.Washington University School of MedicineSt LouisUSA
  2. 2.University of WisconsinMadisonUSA
  3. 3.Gundersen Clinic, Ltd.La CrosseUSA
  4. 4.Mayo Clinic RochesterRochesterUSA
  5. 5.Minnesota Oncology HematologyMinneapolisUSA
  6. 6.Center for Cancer Care and ResearchSt LouisUSA
  7. 7.Mayo Clinic Cancer CenterRochesterUSA

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