Ramalingam Suresh S, Belani Chandra P, Ruel Christopher, Frankel Paul, Gitlitz Barbara, Koczywas Marianna, Espinoza-Delgado Igor, Gandara David
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.
J Thorac Oncol. 2009 Jan;4(1):97-101. doi: 10.1097/JTO.0b013e318191520c.
Belinostat (PXD 101) is a novel inhibitor of class I and II histone deacetylases. This class of compounds has demonstrated anticancer activity in malignant mesothelioma. We conducted a phase II study of belinostat in patients with relapsed malignant pleural mesothelioma.
Patients with advanced mesothelioma, progression with one prior chemotherapy regimen and Eastern Cooperative Oncology Group performance status 0-2 were eligible. Belinostat was administered at 1000 mg/m intravenously over 30 minutes on days 1-5 of every 3 week cycle. The primary end point was response rate. The Simon two-stage design was used. Disease assessments were performed every two cycles.
Thirteen patients were enrolled. Baseline characteristics were: median age of 73 years; Eastern Cooperative Oncology Group performance status 0 (n = 4), 1 (8) and 2 (1). A median of two cycles of therapy were administered. Disease stabilization was seen in two patients. No objective responses were noted and the study did not meet criteria to proceed to the second stage of accrual. Median survival was 5 months with a median progression-free survival of 1 month. Salient toxicities included nausea, emesis, fatigue, and constipation. One patient died as a consequence of cardiac arrhythmia which was deemed 'possibly' related to therapy.
Belinostat is not active as monotherapy against recurrent malignant pleural mesothelioma. Evaluation of combination strategies or alternate dosing schedules may be necessary for further development of this novel agent in mesothelioma.
贝利司他（PXD 101）是一种新型的I类和II类组蛋白去乙酰化酶抑制剂。这类化合物已在恶性间皮瘤中显示出抗癌活性。我们开展了一项贝利司他治疗复发性恶性胸膜间皮瘤患者的II期研究。
符合条件的患者为患有晚期间皮瘤、对一种既往化疗方案有进展且东部肿瘤协作组体能状态为0 - 2的患者。在每3周周期的第1 - 5天，以1000 mg/m²的剂量静脉输注贝利司他，持续30分钟。主要终点为缓解率。采用西蒙两阶段设计。每两个周期进行一次疾病评估。
共纳入13例患者。基线特征为：中位年龄73岁；东部肿瘤协作组体能状态为0（n = 4）、1（8）和2（1）。中位给予两个周期的治疗。两名患者病情稳定。未观察到客观缓解，该研究未达到进入第二阶段入组的标准。中位生存期为5个月，中位无进展生存期为1个月。主要毒性包括恶心、呕吐、疲劳和便秘。一名患者因心律失常死亡，该心律失常被认为“可能”与治疗有关。
贝利司他作为单药治疗复发性恶性胸膜间皮瘤无效。对于这种新型药物在间皮瘤中的进一步研发，可能需要评估联合策略或交替给药方案。
