Duvic Madeleine, Olsen Elise A, Breneman Debra, Pacheco Theresa R, Parker Sareeta, Vonderheid Eric C, Abuav Rachel, Ricker Justin L, Rizvi Syed, Chen Cong, Boileau Kathleen, Gunchenko Alexandra, Sanz-Rodriguez Cesar, Geskin Larisa J
Department of Dermatology, The University of Texas M. D. Anderson Cancer Center, Box 1492, 1515 Holcombe Blvd, Houston, TX 77030, USA.
Clin Lymphoma Myeloma. 2009 Dec;9(6):412-6. doi: 10.3816/CLM.2009.n.082.
Vorinostat, an orally active histone deacetylase inhibitor, was approved in October 2006 by the US Food and Drug Administration for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma (CTCL) in patients with progressive, persistent, or recurrent disease during or after treatment with 2 systemic therapies.
A multicenter, open-label phase IIb trial evaluated the activity and safety of vorinostat 400 mg orally daily in patients with > or = stage IB, persistent, progressive, or treatment-refractory mycosis fungoides or Sézary syndrome CTCL subtypes. We report the safety and tolerability of long-term vorinostat therapy in patients who experienced clinical benefit in the previous phase IIb study.
As of December 11, 2008, 6 of 74 patients enrolled in the original study had received vorinostat for > or = 2 years: median age, 65 years; median number of previous therapies, 2.5; median time from diagnosis to enrollment, 1.8 years. At enrollment into the continuation phase, 5 of the 6 patients had achieved an objective response, and 1 patient had prolonged stable disease. During the follow-up study, the most common drug-related grade 1-4 adverse events (AEs) were diarrhea, nausea, fatigue, and alopecia (6, 5, 4, and 3 patients, respectively). Incidence of grade 3/4 AEs was low: anorexia (n = 1), increased creatinine phosphokinase (n = 1), pulmonary embolism (n = 1), rash (n = 1), and thrombocytopenia (n = 1). Five patients have discontinued the study drug, and 1 patient is continuing therapy.
This post hoc subset analysis provides evidence for the long-term safety and clinical benefit of vorinostat in heavily pretreated patients with CTCL, regardless of previous treatment failures.
伏立诺他是一种口服活性组蛋白脱乙酰酶抑制剂，于2006年10月被美国食品药品监督管理局批准用于治疗皮肤T细胞淋巴瘤（CTCL）的皮肤表现，适用于在接受两种全身治疗期间或之后出现进展性、持续性或复发性疾病的患者。
一项多中心、开放标签的IIb期试验评估了每日口服400 mg伏立诺他对IB期及以上、持续性、进展性或治疗难治性蕈样肉芽肿或 Sézary 综合征CTCL亚型患者的活性和安全性。我们报告了在前一项IIb期研究中获得临床益处的患者长期使用伏立诺他治疗的安全性和耐受性。
截至2008年12月11日，原研究纳入的74例患者中有6例接受伏立诺他治疗≥2年：中位年龄65岁；既往治疗的中位次数为2.5次；从诊断到入组的中位时间为1.8年。进入延续期时，6例患者中有5例获得了客观缓解，1例患者疾病稳定期延长。在随访研究中，最常见的1-4级药物相关不良事件（AE）为腹泻、恶心、疲劳和脱发（分别为6例、5例、4例和3例患者）。3/4级AE的发生率较低：厌食（n = 1）、肌酸磷酸激酶升高（n = 1）、肺栓塞（n = 1）、皮疹（n = 1）和血小板减少（n = 1）。5例患者已停用研究药物，1例患者仍在继续治疗。
这项事后亚组分析为伏立诺他在经过大量预处理的CTCL患者中的长期安全性和临床益处提供了证据，无论既往治疗是否失败。
