Potential role of histone deacetylase inhibitors in mesothelioma: Clinical experience with suberoylanilide hydroxamic acid Journal Article

  


Authors: Krug, L. M.; Curley, T.; Schwartz, L.; Richardson, S.; Marks, P.; Chiao, J.; Kelly, W. K.
Article Title: Potential role of histone deacetylase inhibitors in mesothelioma: Clinical experience with suberoylanilide hydroxamic acid
Abstract: 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 mesothelloma 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 ther apy; 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.
Keywords: adult; cancer chemotherapy; clinical article; controlled study; treatment outcome; aged; middle aged; treatment failure; unclassified drug; histone deacetylase inhibitor; clinical trial; constipation; fatigue; neutropenia; bevacizumab; cisplatin; doxorubicin; advanced cancer; cancer growth; diarrhea; gemcitabine; anorexia; carboplatin; controlled clinical trial; drug eruption; infection; cohort studies; anemia; leukopenia; nausea; thrombocytopenia; dehydration; drug administration schedule; tomography, x-ray computed; antineoplastic activity; hyperglycemia; chemotherapy induced emesis; drug fatality; enzyme inhibitors; drug response; experience; mesothelioma; vorinostat; hydroxamic acids; phase 1 clinical trial; corticosteroid; navelbine; administration, oral; pemetrexed; histone deacetylases; pleural neoplasms; pralatrexate; computed tomography; epothilone derivative; suberoylanilide hydroxamic acid; aminopterin derivative
Journal Title: Clinical Lung Cancer
Volume: 7
Issue: 4
ISSN: 1525-7304
Publisher: Elsevier Inc.  
Date Published: 2006-01-01
Start Page: 257
End Page: 261
Language: English
PUBMED: 16512979
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-33244458274&partnerID=40&md5=b4011a781ebac8c392ff8d4794993ad2
Notes: --- - "Cited By (since 1996): 87" - "Export Date: 4 June 2012" - "CODEN: CLCLC" - "Source: Scopus"
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MSK Authors
  1. Lee M Krug
    178 Krug
  2. William K Kelly
    115 Kelly
  3. Lawrence H Schwartz
    306 Schwartz
  4. Tracy B Smart-Curley
    70 Smart-Curley
  5. Paul Marks
    186 Marks
  6. Stacie Richardson
    5 Richardson
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