Phase I study of MGCD0103 given as a three-times-per-week oral dose in patients with advanced solid tumors.

ABSTRACT:

Purpose

MGCD0103 is a novel isotype-selective inhibitor of human histone deaceylases (HDACs) with the potential to regulate aberrant gene expression and restore normal growth control in malignancies.

Patients and methods

A phase I trial of MGCD0103, given as a three-times-per-week oral dose for 2 of every 3 weeks, was performed in patients with advanced solid tumors. Primary end points were safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD) assessments of HDAC activity, and histone acetylation status in peripheral WBCs.

Results

Six dose levels ranging from 12.5 to 56 mg/m(2)/d were evaluated in 38 patients over 99 cycles (median, 2; range, 1 to 11). The recommended phase II dose was 45 mg/m(2)/d. Dose-limiting toxicities consisting of fatigue, nausea, v

SUBMITTER: Siu LL 

PROVIDER: S-EPMC3501257 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature