Publication Date:
2008-11-16
Description:
Rationale and goal: Gene silencing that occurs as a result of histone deacetylation and subsequent block in cell differentiation is considered an important leukemogenic process. Reinstatement of gene expression through modulation of histone acetylation may be an important therapeutic approach for leukemia. Phase 1 and 2 studies with vorinostat, a potent histone deacetylase (HDAC) inhibitor, have suggested that vorinostat can induce histone acetylation in vivo, and anti-tumor activities against advanced solid tumors and hematologic malignancies have been reported. Our goal was to design a phase 1 trial of vorinostat combined with drugs active in acute myeloid leukemia (AML). Study design: Based on our preclinical work showing that cytarabine (ara-C) and vorinostat are antagonistic when given concomitantly but that ara-C and etoposide are synergistic with vorinostat when given after vorinostat exposure at proper dose ranges (Proc AACR2006, 47: abstract 2122), we designed a clinical study with escalating doses of vorinostat given orally on days 1–7, followed by ara-C (1gm/m2 q12h IV over 3h if age ≥65, 2 gm/m2 q12h IV over 3h if age
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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