Potential role of histone deacetylase inhibitors in mesothelioma: clinical experience with suberoylanilide hydroxamic Acid

Clinical Lung Cancer. 2006 Jan;7(4):257-61. [Link]

Krug LM, Curley T, Schwartz L, Richardson S, Marks P, Chiao J, Kelly WK.

Thoracic Oncology Service , Memorial Sloan-Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY ; e-mail: krugl@mskcc.org.


Background: Histone deacetylase inhibitors are a novel class of therapeutic agents that inhibit deacetylate histones and other proteins involved in the regulation of gene expression and cell cycle progression. Phase I trials of intravenous and oral formulations of one such agent, vorinostat (suberoylanilide hydroxamic acid [SAHA]), have shown that it is safe and tolerable, that it inhibits histone deacetylation in peripheral blood mononuclear cells, and that it has a broad range of antitumor activity.

Patients and Methods: Thirteen patients with mesothelioma were included in a phase I trial of oral SAHA. All but one had previously been treated with chemotherapy.

Results: Four patients completed >/= 6 cycles of therapy; 2 patients demonstrated a partial response. The toxicities in this cohort of patients were similar to those observed in the entire phase I trial: primarily fatigue, dehydration, nausea, and vomiting.

Conclusion: Given the dearth of treatment options for patients with advanced mesothelioma who have progressed after first-line chemotherapy, these results are encouraging. A placebo-controlled, randomized phase III study of oral SAHA is now open for patients with mesothelioma in whom treatment with pemetrexed has failed.