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

Clin Lung Cancer. 2006 Jan;7(4):257-61. doi: 10.3816/CLC.2006.n.003.


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 > or = 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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Cohort Studies
  • Drug Administration Schedule
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Histone Deacetylase Inhibitors*
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Male
  • Mesothelioma / diagnostic imaging
  • Mesothelioma / drug therapy*
  • Mesothelioma / pathology
  • Middle Aged
  • Pleural Neoplasms / diagnostic imaging
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / pathology
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vorinostat


  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Hydroxamic Acids
  • Vorinostat