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

6607 Background: Inhibition of HDAC can induce differentiation, growth arrest, and apoptosis in cancer cells. Belinostat (PXD101) is a potent inhibitor of both class I and class II HDAC enzymes. This phase II study was undertaken to estimate the efficacy of belinostat for the treatment of MDS. Methods: Adults with MDS (any WHO classification, plus at least 1 significant cytopenia if < 5% bone marrow blasts) were eligible if they had ≤ 2 prior therapies for MDS, adequate renal and hepatic function, and ECOG 0-2. The primary endpoint was proportion of confirmed responses (CR, PR, and hematologic improvement [HI]) during the first 12 wks of treatment. Patients were treated with belinostat 1,000 mg/m2 as a 30 min IV infusion on days 1-5 of a 21 day cycle for 4 cycles. Responding pts could receive additional cycles until disease progression or unacceptable toxicity. 21 pts were to be enrolled in the first stage, and if 3 or more responses were observed, an additional 29 would be enrolled in stage 2. Results: 2...