Blood Test Measures Cancer Drug Efficacy

The blood test evaluates whether changes in circulating blood cells is reflected by the activity of the histone deacetylase (HDAC) inhibitor which could be detected.

Clinical benefit from use of a novel histone deacetylase-inhibitor drug may be determined by examining blood cells days after a patient receives treatment. The drug entinostat was the first histone deacetylase inhibitor successfully tested in a randomized, placebo-controlled study in metastatic breast cancer, and is the first to show that clinical outcome can be predicted shortly after administration.

Scientists at Syndax Pharmaceuticals (Waltham MA, USA) conducted a randomized, placebo-controlled, phase II study on 130 patients with estrogen-receptor (ER)-positive metastatic breast cancer, testing the use of an aromatase inhibitor, with either the HDAC inhibitor or a placebo. Results of the clinical trial showed that the combination therapy delayed cancer progression by 27% compared with aromatase inhibitor (exemestane) treatment alone.

In a subset analysis, scientists examined blood samples from 49 patients, (27 of whom had received combination therapy) to evaluate whether changes in circulating blood cells that reflected the activity of the histone deacetylase (HDAC) inhibitor could be detected. They measured protein lysine acetylation, a biological marker of entinostat activity, in B cells, T cells and monocytes in blood samples taken at pretreatment and one, eight and 15 days after therapy with entinostat, which is taken once a week.

While levels of lysine acetylation after one day were not linked to clinical benefit, levels measured eight and 15 days after therapy were related to clinical benefit. Patients with elevated levels of protein lysine acetylation had a 68% reduced risk for disease progression compared with those patients who did not have sustained elevated levels. Peter Ordentlich, PhD, a founder of Syndax Pharmaceuticals, said, "Entinostat's long half-life and unique pharmacology allow researchers to quickly gauge the agent's activity. In this way, we gain insight into how to use HDAC inhibitors, as a class of cancer drugs, in a variety of solid tumors." The results of the study were presented at an International Conference on Molecular Targets and Cancer Therapeutics held November 12-16, 2011, in San Francisco CA, USA).

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