Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma, (CTCL)
Phase 2 trial of oral vorinostat (suberoylanilide hydroxamic acid, SAHA) for refractory cutaneous T-cell lymphoma, (CTCL)
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DOI：
10.1182/blood-2006-06-025999
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发表时间：
2007-01-01
期刊：
影响因子：
20.3
通讯作者：
Frankel, Stanley R.
中科院分区：
文献类型：
--
作者：
Duvic, Madeleine;Talpur, Rakshandra;Frankel, Stanley R.
在难治性皮肤T细胞淋巴瘤（CTCL）患者中评价了组蛋白去乙酰化酶抑制剂伏立诺他（辛二酰苯胺异羟肟酸，SAHA）的活性和安全性。第1组接受伏立诺他400 mg每日一次，第2组接受伏立诺他300 mg每日两次，持续3天，停药4天，第3组接受伏立诺他300 mg每日两次，持续14天，停药7天，随后接受200 mg每日两次。治疗持续至疾病进展或出现不可耐受的毒性。主要目的是确定完全和部分缓解（PR）率。确定至缓解时间（TTR）、至疾病进展时间（TTP）、缓解持续时间（DOR）、瘙痒缓解和安全性。入组了33例既往接受过中位5种治疗的患者。8例患者达到PR，包括7例晚期疾病和4例Sezary综合征。应答者的中位TTR、DOR和TTP分别为11.9、15.1和30.2周。31例可评价患者中有14例瘙痒缓解。最常见的药物相关AE为疲乏、血小板减少、腹泻和恶心。最常见的3级或4级药物相关AE为血小板减少症和脱水。伏立诺他在大量预先治疗的CTCL患者中表现出活性。每日400 mg方案具有最有利的安全性特征，正在进一步评估。
The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sezary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pre-treated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated.