Phase II Study of Belinostat in Patients With Recurrent or Refractory Advanced Thymic Epithelial Tumors
Phase II Study of Belinostat in Patients With Recurrent or Refractory Advanced Thymic Epithelial Tumors
复制标题
DOI：
10.1200/jco.2010.32.4467
复制
发表时间：
2011-05-20
影响因子：
45.3
通讯作者：
Loehrer, Patrick J., Sr.
中科院分区：
文献类型：
--
作者：
Giaccone, Giuseppe;Rajan, Arun;Loehrer, Patrick J., Sr.
胸腺上皮性肿瘤是一种罕见的恶性肿瘤，对于化疗失败的晚期患者没有标准的治疗方法。组蛋白去乙酰化酶（HDAC）抑制剂在这种疾病中的抗肿瘤活性已被记录，包括一名患者胸腺瘤治疗泛HDAC抑制剂belinostat.Patients和MethodsPatients晚期胸腺上皮恶性肿瘤中，至少有一行含铂化疗失败有资格参加这项研究。其他合格性标准包括充分的器官功能和良好的体能状态。贝利司他在21天周期的第1 - 5天以1 g/m2静脉给药，直至疾病进展或出现不耐受。主要目标是响应率与thymoma.ResultsOf 41例患者入组，25胸腺瘤，和16胸腺癌;患者有两个以前的系统方案（范围，1至10方案）的中位数。治疗耐受性良好，恶心、呕吐和疲劳是最常见的不良反应。2例患者达到部分缓解（均患有胸腺瘤;缓解率为8%; 95%CI为2.2%-25%），25例患者病情稳定，13例患者病情进展;胸腺癌患者无缓解。中位进展时间和生存期分别为5.8和19.1个月。胸腺瘤患者的生存期明显长于胸腺癌患者（中位数未达到12.4个月; P = 0.001）。蛋白质乙酰化，调节T细胞数量，和循环血管生成因子没有预测outcome.ConclusionBelinostat有适度的抗肿瘤活性，在这组重度预处理胸腺恶性肿瘤。然而，反应和疾病稳定的持续时间是令人感兴趣的，并且有必要在这种疾病中对贝利司他进行额外的测试。
PurposeThymic epithelial tumors are rare malignancies, and there is no standard treatment for patients with advanced disease in whom chemotherapy has failed. Antitumor activity of histone deacetylase (HDAC) inhibitors in this disease has been documented, including one patient with thymoma treated with the pan-HDAC inhibitor belinostat.Patients and MethodsPatients with advanced thymic epithelial malignancies in whom at least one line of platinum-containing chemotherapy had failed were eligible for this study. Other eligibility criteria included adequate organ function and good performance status. Belinostat was administered intravenously at 1 g/m(2) on days 1 to 5 of a 21-day cycle until disease progression or development of intolerance. The primary objective was response rate in patients with thymoma.ResultsOf the 41 patients enrolled, 25 had thymoma, and 16 had thymic carcinoma; patients had a median of two previous systemic regimens (range, one to 10 regimens). Treatment was well tolerated, with nausea, vomiting, and fatigue being the most frequent adverse effects. Two patients achieved partial response (both had thymoma; response rate, 8%; 95% CI, 2.2% to 25%), 25 had stable disease, and 13 had progressive disease; there were no responses among patients with thymic carcinoma. Median times to progression and survival were 5.8 and 19.1 months, respectively. Survival of patients with thymoma was significantly longer than that of patients with thymic carcinoma (median not reached v 12.4 months; P = .001). Protein acetylation, regulatory T-cell numbers, and circulating angiogenic factors did not predict outcome.ConclusionBelinostat has modest antitumor activity in this group of heavily pretreated thymic malignancies. However, the duration of response and disease stabilization is intriguing, and additional testing of belinostat in this disease is warranted.