Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma
Phase II Trial of Combination Therapy With Bortezomib, Pegylated Liposomal Doxorubicin, and Dexamethasone in Patients With Newly Diagnosed Myeloma
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DOI：
10.1200/jco.2008.19.5370
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发表时间：
2009-10-20
影响因子：
45.3
通讯作者：
Kaminski, Mark S.
中科院分区：
文献类型：
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作者：
Jakubowiak, Andrzej J.;Kendall, Tara;Kaminski, Mark S.
目的这项单中心、开放标签、II 期试验评估了硼替佐米、聚乙二醇化脂质体阿霉素 (PLD) 和地塞米松联合方案 (VDD) 作为新诊断的多发性骨髓瘤 (MM) 患者的初始治疗。 患者和方法 入组患者 (N = 40) 接受了最多 6 个为期 3 周的周期的硼替佐米 1.3 mg/m(2) 静脉注射 (IV) 治疗。第 1、4、8 和 11 天；第 4 天 PLD 30 mg/m2 IV；地塞米松每日 20 至 40 毫克，如研究设计中指定。主要终点是六个周期后的完全/接近完全缓解（CR/nCR）率。次要终点包括总体缓解率（ORR）、无进展生存期（PFS）和总体生存期（OS）。还评估了 VDD 对干细胞动员和收集的影响。结果六个周期后，ORR 为 85.0%（CR/nCR，37.5%；非常好的部分缓解 [VGPR] 或更好，57.5%）。 VDD 后接受干细胞移植 (SCT) 的患者 (n = 30) 的 VGPR 率增加或更好（SCT 后从 53.3% 升至 76.6%）。总体而言，1 年 PFS 和 OS 率分别为 92.5% 和 97.5%。与那些未达到 VGPR 的患者相比，使用 VDD 治疗后达到 VGPR 或更好的患者的 1 年 PFS 显着更高（分别为 100% 和 82%；P = .03）。在接受 SCT 的患者中也观察到了类似的结果。 3级或4级血液学毒性发生在
PurposeThis single-center, open-label, phase II trial evaluated the bortezomib, pegylated liposomal doxorubicin (PLD), and dexamethasone combination regimen (VDD) as initial treatment for patients with newly diagnosed multiple myeloma (MM).Patients and MethodsEnrolled patients (N = 40) received up to six 3-week cycles of treatment with bortezomib 1.3 mg/m(2) intravenously (IV) on days 1, 4, 8, and 11; PLD 30 mg/m2 IV on day 4; and dexamethasone 20 to 40 mg daily as specified in the study design. The primary end point was the complete/near-complete response (CR/nCR) rate after six cycles. Secondary end points included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The impact of VDD on stem-cell mobilization and collection also was evaluated.ResultsAfter six cycles, the ORR was 85.0% (CR/nCR, 37.5%; very good partial response [VGPR] or better, 57.5%). Patients who underwent stem-cell transplantation (SCT) after VDD (n = 30) experienced increased rates of VGPR or better (53.3% to 76.6% after SCT). Overall, 1-year PFS and OS rates were 92.5% and 97.5%, respectively. Those who achieved VGPR or better after treatment with VDD showed a significantly greater 1-year PFS versus those who achieved less than VGPR (100% v 82%, respectively; P = .03). Similar results were observed in patients who underwent SCT. Grades 3 or 4 hematologic toxicities occurred in