Hackensack University Medical Center, Hackensack, NJ, USA.
J Hematol Oncol. 2009 Jul 27;2:31. doi: 10.1186/1756-8722-2-31.
Vorinostat (Zolinza), a histone deacetylase inhibitor, was approved by the US Food and Drug Administration in October 2006 for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following two systemic therapies. This review summarizes evidence on the use of vorinostat in solid and hematologic malignancies and collated tolerability data from the vorinostat clinical trial program. Pooled vorinostat clinical trial data from 498 patients with solid or hematologic malignancies show that vorinostat was well tolerated as monotherapy or combination therapy. The most commonly reported drug-related adverse events (AEs) associated with monotherapy (n = 341) were fatigue (61.9%), nausea (55.7%), diarrhea (49.3%), anorexia (48.1%), and vomiting (32.8%), and Grade 3/4 drug-related AEs included fatigue (12.0%), thrombocytopenia (10.6%), dehydration (7.3%), and decreased platelet count (5.3%). The most common drug-related AEs observed with vorinostat in combination therapy (n = 157, most of whom received vorinostat 400 mg qd for 14 days) were nausea (48.4%), diarrhea (40.8%), fatigue (34.4%), vomiting (31.2%), and anorexia (20.4%), with the majority of AEs being Grade 2 or less. In Phase I trials, combinations with vorinostat were generally well tolerated and preliminary evidence of anticancer activity as monotherapy or in combination with other systemic therapies has been observed across a range of malignancies. Ongoing and planned studies will further evaluate the potential of vorinostat in combination therapy, including combinations with radiation, in patients with diverse malignancy types, including non-small-cell lung cancer, glioblastoma multiforme, multiple myeloma, and myelodysplastic syndrome.
伏立诺他（Zolinza），一种组蛋白去乙酰化酶抑制剂，于 2006 年 10 月获得美国食品和药物管理局批准，用于治疗患有皮肤 T 细胞淋巴瘤的患者，这些患者在接受两种全身治疗后或治疗后出现进行性、持续性或复发性疾病，且这两种治疗方法均无效。本综述总结了伏立诺他在实体瘤和血液恶性肿瘤中的应用证据，并整理了来自伏立诺他临床试验项目的耐受性数据。来自 498 例患有实体瘤或血液恶性肿瘤的患者的伏立诺他临床试验汇总数据表明，伏立诺他作为单药或联合治疗具有良好的耐受性。单药治疗（n=341）最常报告的药物相关不良事件（AE）为疲劳（61.9%）、恶心（55.7%）、腹泻（49.3%）、厌食（48.1%）和呕吐（32.8%），3/4 级药物相关 AE 包括疲劳（12.0%）、血小板减少症（10.6%）、脱水（7.3%）和血小板计数减少（5.3%）。在联合治疗中观察到的与伏立诺他相关的最常见药物相关 AE（n=157，其中大多数患者接受伏立诺他 400mg qd 治疗 14 天）为恶心（48.4%）、腹泻（40.8%）、疲劳（34.4%）、呕吐（31.2%）和厌食（20.4%），大多数 AE 为 2 级或更低级别。在 I 期试验中，与伏立诺他联合使用通常具有良好的耐受性，并且在一系列恶性肿瘤中观察到作为单药或与其他全身治疗联合使用的初步抗癌活性的证据。正在进行和计划中的研究将进一步评估伏立诺他联合治疗的潜力，包括与放疗联合治疗，用于多种恶性肿瘤类型的患者，包括非小细胞肺癌、多形性胶质母细胞瘤、多发性骨髓瘤和骨髓增生异常综合征。
