Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health/DHHS, 6130 Executive Blvd., Rockville, MD 20852, USA.
Blood. 2011 Jun 2;117(22):5827-34. doi: 10.1182/blood-2010-10-312603. Epub 2011 Feb 25.
Romidepsin (depsipeptide or FK228) is a histone deacetylase inhibitor, one of a new class of agents active in T-cell lymphoma. A phase 2 trial was conducted in cutaneous (CTCL) and peripheral (PTCL) T-cell lymphoma. Major and durable responses in CTCL supported the approval of romidepsin for CTCL. Forty-seven patients with PTCL of various subtypes including PTCL NOS, angioimmunoblastic, ALK-negative anaplastic large cell lymphoma, and enteropathy-associated T-cell lymphoma were enrolled. All patients had received prior therapy with a median of 3 previous treatments (range 1-11); 18 (38%) had undergone stem-cell transplant. All patients were evaluated for toxicity; 2 patients discovered to be ineligible were excluded from response assessment. Common toxicities were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. Complete responses were observed in 8 and partial responses in 9 of 45 patients, for an overall response rate of 38% (95% confidence interval 24%-53%). The median duration of overall response was 8.9 months (range 2-74). Responses were observed in various subtypes, with 6 responses among the 18 patients with prior stem-cell transplant. The histone deacetylase inhibitor romidepsin has single agent clinical activity associated with durable responses in patients with relapsed PTCL.
罗米地辛(去乙酰化酶抑制剂或 FK228)是一种组蛋白去乙酰化酶抑制剂,属于在 T 细胞淋巴瘤中具有活性的新型药物之一。一项针对皮肤(CTCL)和外周(PTCL)T 细胞淋巴瘤的 2 期试验已经进行。在 CTCL 中观察到主要和持久的反应,这支持了罗米地辛在 CTCL 中的批准。47 名患有各种亚型的 PTCL 患者(包括 PTCLNOS、血管免疫母细胞性、ALK 阴性间变性大细胞淋巴瘤和肠病相关 T 细胞淋巴瘤)入组。所有患者均接受过先前的治疗,中位数为 3 次先前治疗(范围 1-11);18 名(38%)接受过干细胞移植。所有患者均进行了毒性评估;2 名发现不符合条件的患者被排除在反应评估之外。常见的毒性包括恶心、疲劳、短暂的血小板减少和粒细胞减少。45 名患者中有 8 名完全缓解,9 名部分缓解,总缓解率为 38%(95%置信区间 24%-53%)。总缓解的中位持续时间为 8.9 个月(范围 2-74)。在各种亚型中均观察到缓解,18 名有干细胞移植史的患者中有 6 名出现缓解。组蛋白去乙酰化酶抑制剂罗米地辛在复发性 PTCL 患者中具有单药临床活性,并与持久缓解相关。