Phase 1 study of oral abexinostat, a histone deacetylase inhibitor, in combination with doxorubicin in patients with metastatic sarcoma.

ABSTRACT:

Background

It has been demonstrated that several inhibitors of histone deacetylase (HDAC) can enhance chemotherapy-induced apoptosis and reduce sarcoma tumor volume in preclinical models. The authors sought to determine the maximum tolerated dose, pharmacokinetics/pharmacodynamics, safety, and toxicity of the HDAC inhibitor abexinostat (PCI-24781) when administered with doxorubicin to patients with metastatic sarcomas.

Methods

Participants were enrolled in a standard, phase 1, 3 + 3, dose-escalation study design. Abexinostat was administered on days 1 through 5 with 75 mg/m(2) of doxorubicin administered on day 4 of every 21-day cycle until patients developed disease progression or drug intolerance or reached a cumulative lifetime doxorubicin dose of 450 mg/m(2). Granulocyte

SUBMITTER: Choy E 

PROVIDER: S-EPMC4393337 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature