A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma
A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma
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DOI：
10.1111/bjh.13222
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发表时间：
2015-03-01
影响因子：
6.5
通讯作者：
Pohlman, Brad
中科院分区：
文献类型：
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作者：
Foss, Francine;Advani, Ranjana;Pohlman, Brad
贝利司他是具有抗肿瘤和抗血管生成特性的泛组蛋白脱乙酰酶抑制剂。在1次既往全身治疗失败并接受贝利司他（1000 mg/m2，静脉注射，每21天为1个周期，共5天）治疗的外周T细胞淋巴瘤（PTCL）或皮肤T细胞淋巴瘤（CTCL）患者中进行了一项开放标签、多中心研究。主要终点为客观缓解率（ORR）。PTCL患者（n=24）接受过中位3种既往全身治疗（范围1-9），40%的患者患有IV期疾病。CTCL患者（n=29）接受过中位1次既往皮肤定向治疗（范围0-4）和4次既往全身治疗（范围1-9）; 55%的患者为IV期疾病。ORR分别为25%（PTCL）和14%（CTCL）。77%的患者发生了治疗相关不良事件;恶心（43%）、呕吐（21%）、输注部位疼痛（13%）和头晕（11%）的发生率最高。治疗相关严重不良事件为5级室颤; 4级血小板减少症; 3级外周水肿、失用症、麻痹性肠梗阻和肺炎; 2级颈静脉血栓形成。贝利司他单药治疗在复发性/难治性PTCL和CTCL患者中耐受性良好且有效。本试验注册为NCT 00274651。
Belinostat is a pan-histone deacetylase inhibitor with antitumour and anti-angiogenic properties. An open label, multicentre study was conducted in patients with peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL) who failed 1 prior systemic therapy and were treated with belinostat (1000mg/m(2) intravenously x5d of a 21-d cycle). The primary endpoint was objective response rate (ORR). Patients with PTCL (n=24) had received a median of three prior systemic therapies (range 1-9) and 40% had stage IV disease. Patients with CTCL (n=29) had received a median of one prior skin-directed therapy (range 0-4) and four prior systemic therapies (range 1-9); 55% had stage IV disease. The ORRs were 25% (PTCL) and 14% (CTCL). Treatment-related adverse events occurred in 77% of patients; nausea (43%), vomiting (21%), infusion site pain (13%) and dizziness (11%) had the highest incidence. Treatment-related serious adverse events were Grade 5 ventricular fibrillation; Grade 4 thrombocytopenia; Grade 3 peripheral oedema, apraxia, paralytic ileus and pneumonitis; and Grade 2 jugular vein thrombosis. Belinostat monotherapy was well tolerated and efficacious in patients with recurrent/refractory PTCL and CTCL. This trial was registered at as NCT00274651.