文章：

伏立诺他联合来那度胺和地塞米松治疗复发或难治性多发性骨髓瘤

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma

原文发布日期：2014-02-21

DOI: 10.1038/bcj.2014.1

类型: Original Article

开放获取: 是

英文摘要：

The addition of vorinostat to lenalidomide/dexamethasone represents a novel combination therapy in multiple myeloma (MM), informed by laboratory studies suggesting synergy. This was a phase I, multicenter, open-label, non-randomized, dose-escalating study in patients with relapsed or relapsed and refractory MM. Clinical evaluation, electrocardiogram, laboratory studies and adverse events were obtained and assessed. The maximum-tolerated dose was not reached owing to a non-occurrence of two dose-limiting toxicities per six patients tested at any of the dosing levels. Patients tolerated the highest dose tested (Level 5) and this was considered the maximum administered dose: at 400 mg vorinostat on days 1–7 and 15–21, 25 mg lenalidomide on days 1–21 and 40 mg dexamethasone on days 1, 8, 15 and 22, per 28-day cycle. Drug-related adverse events were reported in 90% of patients serious adverse experiences were reported in 45% of the patients and 22% of all patients had adverse experiences considered, possibly related to study drug by the investigators. A confirmed partial response or better was reported for 14/30 patients (47%) evaluable for efficacy, including 31% of patients previously treated with lenalidomide. Vorinostat in combination with lenalidomide and dexamethasone proved tolerable with appropriate supportive care, with encouraging activity observed.

摘要翻译： 

伏立诺他联合来那度胺/地塞米松是一种基于实验室研究提示协同作用的多发性骨髓瘤新型联合疗法。本研究为一项针对复发或复发难治性多发性骨髓瘤患者的I期、多中心、开放标签、非随机化、剂量递增试验。研究收集并评估了患者的临床评估、心电图、实验室检查及不良事件。由于在任何剂量水平下，每6例受试患者均未出现2例剂量限制性毒性，故未达到最大耐受剂量。患者耐受住了测试最高剂量（水平5），该剂量被视为最大给药剂量：每28天周期中，第1-7天和第15-21天服用伏立诺他400mg，第1-21天服用来那度胺25mg，第1、8、15、22天服用地塞米松40mg。90%的患者报告了药物相关不良事件，45%的患者报告了严重不良体验，22%的患者出现研究者认为可能与研究药物相关的不良体验。在可评估疗效的30例患者中，14例（47%）确认达到部分缓解或更好疗效，其中包括31%曾接受过来那度胺治疗的患者。研究证实，在适当支持治疗下，伏立诺他联合来那度胺和地塞米松方案耐受性良好，并显示出令人鼓舞的治疗活性。

原文链接：

Vorinostat in combination with lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma