Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma
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DOI：
10.1200/jco.2008.21.6150
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发表时间：
2009-11-10
影响因子：
45.3
通讯作者：
Bates, Susan E.
中科院分区：
文献类型：
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作者：
Piekarz, Richard L.;Frye, Robin;Bates, Susan E.
研究目的罗米地辛（Romidepsin，FK 228）是一种新的治疗T细胞淋巴瘤的药物，是组蛋白去乙酰化酶抑制剂。在I期试验中观察到的反应的基础上，罗米地辛在T细胞淋巴瘤患者的II期试验initiated.Patients和MethodsThe初始队列仅限于皮肤T细胞淋巴瘤（CTCL），或亚型蕈样肉芽肿或Sezary综合征，谁收到了不超过两个先前的细胞毒性方案的患者。对其他类型的治疗没有限制。随后，该协议被扩大到招募患者谁收到了两个以上的前细胞毒性regiments.ResultsTwenty-seven患者被招募到第一个队列，共71例患者被纳入本分析。这些患者接受了中位4次既往治疗，62例患者（87%）患有晚期疾病（IIB期，n = 15; III期，n = 6;或IV期，n = 41）。毒性包括恶心、呕吐、疲劳和一过性血小板减少症和粒细胞减少症。首次给予罗米地辛后评价药代动力学。在4例患者中观察到完全缓解，在20例患者中观察到部分缓解，总缓解率为34%（95% CI，23%至46%）。中位反应持续时间为13.7 months.ConclusionThe组蛋白去乙酰化酶抑制剂romidepsin具有单药临床活性与CTCL患者的显着和持久的反应。
PurposeRomidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated.Patients and MethodsThe initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sezary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens.ResultsTwenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease ( stage IIB, n = 15; stage III, n = 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months.ConclusionThe histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL.