Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma:: Combination therapy improves time to progression
Randomized phase III study of pegylated liposomal doxorubicin plus bortezomib compared with bortezomib alone in relapsed or refractory multiple myeloma:: Combination therapy improves time to progression
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DOI：
10.1200/jco.2006.10.5460
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发表时间：
2007-09-01
影响因子：
45.3
通讯作者：
Harousseau, Jean-Luc
中科院分区：
文献类型：
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作者：
Orlowski, Robert Z.;Nagler, Arnon;Harousseau, Jean-Luc
目的本III期国际研究比较了聚乙二醇脂质体阿霉素（PLD）加硼替佐米与硼替佐米单药治疗复发或难治性多发性骨髓瘤患者的疗效和安全性。患者和方法646例患者被随机分配接受静脉内硼替佐米1.3 mg/m2，每21天为一周期，第1、4、8和11天，结果中位疾病进展时间从硼替佐米治疗的6.5个月增加到PLD +硼替佐米联合治疗的9.3个月（P = 0.00004;风险比，1.82 [单药治疗vs联合治疗]; 95%CI，1.41 - 2.35）。PLD +硼替佐米的15个月生存率为76%，而硼替佐米单独治疗的15个月生存率为65%（P = 0.03）。硼替佐米组的完全加部分缓解率为41%，PLD +硼替佐米组为44%，差异无统计学意义。PLD +硼替佐米的中位缓解持续时间从7.0个月延长至10.2个月（P = 0.0008）。3/ 4级不良事件在联合用药组中更常见（80% v64%），安全性特征与两种药物的已知毒性一致。联合治疗组中3/ 4级中性粒细胞减少、血小板减少、虚弱、疲劳、腹泻和手足综合征的发生率增加。结论PLD联合硼替佐米治疗复发或难治性多发性骨髓瘤患者优于硼替佐米单药治疗的上级疗效。联合治疗与3/ 4级骨髓抑制、全身症状以及GI和皮肤毒性的发生率较高相关。
PurposeThis phase III international study compared the efficacy and safety of a combination of pegylated liposomal doxorubicin ( PLD) plus bortezomib with bortezomib monotherapy in patients with relapsed or refractory multiple myeloma.Patients and MethodsSix hundred forty-six patients were randomly assigned to receive either intravenous bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 of an every 21-days cycle, or the same bortezomib regimen with PLD 30 mg/m(2) on day 4.ResultsMedian time to progression was increased from 6.5 months for bortezomib to 9.3 months with the PLD + bortezomib combination ( P =.000004; hazard ratio, 1.82 [ monotherapy v combination therapy]; 95% CI, 1.41 to 2.35). The 15- month survival rate for PLD + bortezomib was 76% compared with 65% for bortezomib alone ( P =.03). The complete plus partial response rate was 41% for bortezomib and 44% for PLD + bortezomib, a difference that was not statistically significant. Median duration of response was increased from 7.0 to 10.2 months ( P =.0008) with PLD + bortezomib. Grade 3/ 4 adverse events were more frequent in the combination group ( 80% v 64%), with safety profiles consistent with the known toxicities of the two agents. An increased incidence in the combination group was seen of grade 3/ 4 neutropenia, thrombocytopenia, asthenia, fatigue, diarrhea, and hand- foot syndrome.ConclusionPLD with bortezomib is superior to bortezomib monotherapy for the treatment of patients with relapsed or refractory multiple myeloma. The combination therapy is associated with a higher incidence of grade 3/ 4 myelosuppression, constitutional symptoms, and GI and dermatologic toxicities.