Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Japan.
Int J Hematol. 2010 Jul;92(1):118-26. doi: 10.1007/s12185-010-0624-7. Epub 2010 Jun 18.
We conducted a multicenter, open-label study to investigate the safety, efficacy, and pharmacokinetics of lenalidomide in Japanese patients with relapsed or refractory multiple myeloma The study was composed of the "monotherapy phase", a dose-escalation phase, to determine the tolerability to single agent lenalidomide and the "combination phase" to determine the safety and obtain preliminary data on the efficacy of lenalidomide plus dexamethasone. The primary end points were the tolerability to 25 mg lenalidomide and safety. Nine and six patients were enrolled in the monotherapy phase and the combination phase, respectively. Since 25 mg of monotherapy treatment did not satisfy the DLT criteria, this dose was employed in the combination phase. The major adverse event was myelosuppression. At the planned interim analysis (median study duration, 26.3 weeks), grade 3 or grade 4 neutropenia was observed with high frequency (66.7%). However, all adverse events observed were clinically manageable. In the combination cohort, the overall response rate (> or =PR) was 100%. The pharmacokinetics of lenalidomide showed rapid absorption and elimination after both single and multiple doses. In conclusion, 25 mg of lenalidomide was given safely as a single agent or in combination with dexamethasone in Japanese patients. The good efficacy of the combination therapy was also demonstrated in this study.
我们进行了一项多中心、开放性研究，以评估来那度胺在日本复发/难治性多发性骨髓瘤患者中的安全性、疗效和药代动力学。该研究包括“单药治疗阶段”，以确定来那度胺单药治疗的耐受性，和“联合治疗阶段”，以确定安全性并获得来那度胺联合地塞米松的初步疗效数据。主要终点为 25mg 来那度胺的耐受性和安全性。分别有 9 名和 6 名患者入组单药治疗阶段和联合治疗阶段。由于 25mg 单药治疗未满足 DLT 标准，因此该剂量用于联合治疗阶段。主要不良事件为骨髓抑制。在计划的中期分析（研究中位持续时间为 26.3 周）时，观察到高频率的 3 级或 4 级中性粒细胞减少（66.7%）。然而，所有观察到的不良事件均为临床可管理。在联合治疗队列中，总缓解率（>或=PR）为 100%。来那度胺的药代动力学显示单剂量和多剂量给药后均具有快速吸收和消除。总之，25mg 来那度胺在日本患者中单药或与地塞米松联合应用均安全，且联合治疗具有良好的疗效。
