期刊
LEUKEMIA & LYMPHOMA
卷 58, 期 8, 页码 1880-1886出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10428194.2016.1263843
关键词
Abexinostat; HDAC inhibitors; myelodysplastic syndromes; acute myeloid leukemia; acute lymphoid leukemia
资金
- Pharmacyclics LLC
- AbbVie Company
Histone deacetylase (HDAC) inhibitor abexinostat is under investigation for the treatment of various cancers. Epigenetic changes including aberrant HDAC activity are associated with cancers, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and acute lymphoblastic leukemia (ALL). In this phase 1 dose-escalation study, 17 patients with relapsed/refractory higher-risk MDS, AML, or ALL received oral abexinostat (60, 80 [starting dose], 100, or 120mg) twice daily (bid) on Days 1-14 of 21-day cycles. The most common treatment-related grade 3 adverse events were thrombocytopenia (29%) and neutropenia (24%), none of which led to discontinuation. Maximum-tolerated dose was not reached. Of 12 evaluable patients, best response was stable disease in 1 patient. This study was closed due to limited clinical benefit. Future development of oral abexinostat 100mg bid in patients with MDS, AML, or ALL should focus on combination regimens.ISRCTN registry: 99680465
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