Phase I trial of vorinostat and doxorubicin in solid tumours: histone deacetylase 2 expression as a predictive marker.

ABSTRACT:

Background

Histone deacetylase inhibitors (HDACi) can sensitise cancer cells to topoisomerase inhibitors by increasing their access and binding to DNA.

Methods

This phase I trial was designed to determine the toxicity profile, tolerability, and recommended phase II dose of escalating doses of the HDACi vorinostat, with weekly doxorubicin.

Results

In total, 32 patients were treated; vorinostat was dosed at 400, 600, 800, or 1000 mg day(-1) on days 1-3, followed by doxorubicin (20 mg m(-2)) on day 3 for 3 of 4 weeks. Maximal tolerated dose was determined to be 800 mg day(-1) of vorinostat. Dose-limiting toxicities were grade 3 nausea/vomiting (two out of six) and fatigue (one out of six) at 1000 mg day(-1). Non-dose-limiting grade 3/4 toxicities included haematological

SUBMITTER: Munster PN 

PROVIDER: S-EPMC2768109 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature