Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies.

ABSTRACT:

Purpose

The combination of DNA methylation inhibitors and histone deacetylase inhibitors is synergistic in gene expression activation and may overcome platinum resistance. Sequential treatment with azacitidine and valproic acid (VPA) in combination with carboplatin may overcome resistance to platinum-based therapy, and we conducted a phase I trial to assess safety, maximum tolerated dose (MTD), and clinical correlates. Experimental Design Patients with advanced solid tumors refractory to standard therapy were eligible. In cohorts of escalating doses, patients received azacitidine for 5 days from days 1 to 5, VPA for 7 days from days 5 to 11, and carboplatin starting in the second cycle on days 3 and 10. Clinical correlates included evaluation of epigenetic changes, methylation patt

SUBMITTER: Falchook GS 

PROVIDER: S-EPMC3809091 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature