Evaluation of the Long-Term Tolerability and Clinical Benefit of Vorinostat in Patients With Advanced Cutaneous T-Cell Lymphoma

Madeleine Duvic , Elise A. Olsen , Debra Breneman , Theresa R. Pacheco , Sareeta Parker , Eric C. Vonderheid , Rachel Abuav , Justin L. Ricker , Syed Rizvi , Cong Chen , Kathleen Boileau , Alexandra Gunchenko , Cesar Sanz-Rodriguez , Larisa J. Geskin
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引用次数: 88

Abstract

Introduction

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.

Patients and Methods

A multicenter, open-label phase IIb trial evaluated the activity and safety of vorinostat 400 mg orally daily in patients with ≥ 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.

Results

As of December 11, 2008, 6 of 74 patients enrolled in the original study had received vorinostat for ≥ 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.

Conclusion

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.

伏立诺他治疗晚期皮肤t细胞淋巴瘤的长期耐受性和临床疗效评价
vorinostat是一种口服活性组蛋白去乙酰化酶抑制剂,于2006年10月被美国食品和药物管理局批准用于治疗进展性、持续性或复发性皮肤t细胞淋巴瘤(CTCL)患者在接受两种全身治疗期间或之后的皮肤表现。一项多中心、开放标签的IIb期临床试验评估了vorinostat 400mg每日口服治疗≥IB期、持续性、进行性或难治性蕈样真菌病或ssamzary综合征CTCL亚型患者的活性和安全性。我们报告了在之前的IIb期研究中获得临床获益的患者长期伏立他他治疗的安全性和耐受性。结果:截至2008年12月11日,74名患者中有6人接受伏立诺他治疗≥2年:中位年龄为65岁;既往治疗中位数为2.5;从诊断到入组的中位时间为1.8年。在进入继续期时,6例患者中有5例达到客观缓解,1例患者病情长期稳定。在随访研究中,最常见的1-4级药物相关不良事件(ae)是腹泻、恶心、疲劳和脱发(分别为6例、5例、4例和3例)。3/4级不良事件的发生率较低:厌食症(n = 1)、肌酐磷酸激酶升高(n = 1)、肺栓塞(n = 1)、皮疹(n = 1)和血小板减少症(n = 1)。5例患者已停用研究药物,1例患者仍在继续治疗。结论:无论既往治疗失败与否,该事后亚组分析为伏立他在重度术前治疗的CTCL患者中的长期安全性和临床获益提供了证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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