Portal de Periódicos da CAPES

Potential Role of Histone Deacetylase Inhibitors in Mesothelioma: Clinical Experience with Suberoylanilide Hydroxamic Acid

2006; Elsevier BV; Volume: 7; Issue: 4 Linguagem: Inglês

10.3816/clc.2006.n.003

1938-0690

Lee M. Krug, Tracy Curley, Lawrence B. Schwartz, Stacie Richardson, Paul A. Marks, Judy H. Chiao, William K. Kelly,

Peptidase Inhibition and Analysis

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.