Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial
Panobinostat activity in both bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial
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DOI：
10.1016/j.ejca.2012.08.017
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发表时间：
2013-01-01
影响因子：
8.4
通讯作者：
Prince, H. Miles
中科院分区：
文献类型：
--
作者：
Duvic, Madeleine;Dummer, Reinhard;Prince, H. Miles
背景：Panobinostat是一种有效的口服泛去乙酰化酶抑制剂（pan-DACi），可增加参与多种致癌途径的蛋白质的乙酰化。本研究在贝沙罗汀暴露和初治难治性皮肤t细胞淋巴瘤（CTCL）患者中研究了帕比司他。患者和方法：既往接受>= 2全身治疗方案的CTCL亚型蕈样真菌病和seary综合征患者给予panobinostat (20mg)，每周3次。主要目标是总体缓解率（ORR），由皮肤病、淋巴结和脏器受累的综合评估确定。疾病进展定义为未经证实，>=改良严重程度加权评估工具（mSWAT）与最低点相比增加25%。结果：纳入79例贝萨罗汀暴露患者和60例贝萨罗汀初治患者。103例患者（74.1%）观察到基线mSWAT评分降低。在初步分析中，所有患者的ORR为17.3%（贝沙罗汀暴露组和非初始组分别为15.2%和20.0%）。贝沙罗汀暴露组和非初始组的中位无进展生存期分别为4.2和3.7个月。贝萨罗汀暴露患者的中位缓解持续时间为5.6个月，而贝萨罗汀初治患者的中位缓解持续时间在数据截止时未达到。当使用不太严格的进展标准时，观察到额外的反应。最常见的不良事件是血小板减少、腹泻、疲劳和恶心。血小板减少症和中性粒细胞减少症是仅有的3/4级不良事件，在bb0.5 %的患者中是可控的。结论：尽管对疾病进展的定义非常保守，但在贝沙罗汀暴露和初发CTCL患者中，panobinostat显示出可管理的安全性。ClinicalTrials.gov标识符：NCT00425555。(C) 2012 Elsevier Ltd.版权所有。
Background: Panobinostat is a potent, oral pan-deacetylase inhibitor (pan-DACi) that increases the acetylation of proteins involved in multiple oncogenic pathways. Here, panobinostat is studied in bexarotene-exposed and -naive patients with refractory cutaneous T-cell lymphoma (CTCL).Patients and methods: Patients with CTCL subtypes mycosis fungoides and Sezary syndrome who received >= 2 prior systemic therapy regimens received panobinostat (20 mg) three times every week. The primary objective was overall response rate (ORR) as determined by a combined evaluation of skin disease and involvement of lymph node and viscera. Disease progression was defined as an unconfirmed, >= 25% increase in modified Severity Weighted Assessment Tool (mSWAT) compared with nadir.Results: Seventy-nine bexarotene-exposed and 60 bexarotene-naive patients were enrolled. Reductions in baseline mSWAT scores were observed in 103 patients (74.1%). The ORR was 17.3% in all patients in the primary analysis (15.2% and 20.0% in the bexarotene-exposed and -naive groups, respectively). The median progression-free survival was 4.2 and 3.7 months in the bexarotene-exposed and -naive groups, respectively. The median duration of response was 5.6 months in the bexarotene-exposed patients and was not reached at data cutoff in the bexarotene-naive patients. Additional responses were observed when less-stringent progression criteria were used. The most common adverse events were thrombocytopenia, diarrhoea, fatigue and nausea. Thrombocytopenia and neutropenia were the only grade 3/4 adverse events in > 5% of patients and were manageable.Conclusion: Despite a very conservative definition of disease progression, panobinostat demonstrated activity with a manageable safety profile in bexarotene-exposed and -naive CTCL patients. ClinicalTrials.gov Identifier: NCT00425555. (C) 2012 Elsevier Ltd. All rights reserved.