Krug Lee M, Curley Tracy, Schwartz Lawrence, Richardson Stacie, Marks Paul, Chiao Judy, Kelly W Kevin
Thoracic Oncology Service , Memorial Sloan-Kettering Cancer Center and Joan and Sanford Weill Medical College of Cornell University, New York, NY 10021, USA.
Clin Lung Cancer. 2006 Jan;7(4):257-61. doi: 10.3816/CLC.2006.n.003.
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.
Thirteen patients with mesothelioma were included in a phase I trial of oral SAHA. All but one had previously been treated with chemotherapy.
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.
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.
组蛋白去乙酰化酶抑制剂是一类新型治疗药物，可抑制组蛋白及其他参与基因表达调控和细胞周期进程的蛋白质的去乙酰化。一种此类药物伏立诺他（辛二酰苯胺异羟肟酸[SAHA]）的静脉和口服制剂的I期试验表明，它安全且耐受性良好，可抑制外周血单核细胞中的组蛋白去乙酰化，并且具有广泛的抗肿瘤活性。
13例间皮瘤患者纳入口服SAHA的I期试验。除1例患者外，其余患者此前均接受过化疗。
4例患者完成了≥6个周期的治疗；2例患者出现部分缓解。该组患者的毒性与整个I期试验中观察到的毒性相似：主要为疲劳、脱水、恶心和呕吐。
鉴于一线化疗后病情进展的晚期间皮瘤患者治疗选择匮乏，这些结果令人鼓舞。一项口服SAHA的安慰剂对照、随机III期研究目前正在招募培美曲塞治疗失败的间皮瘤患者。
