Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma - A phase III multicenter randomized trial
Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma - A phase III multicenter randomized trial
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DOI：
10.1002/cncr.21662
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发表时间：
2006-02-15
期刊：
影响因子：
6.2
通讯作者：
Hussein, MA
中科院分区：
文献类型：
--
作者：
Rifkin, RM;Gregory, SA;Hussein, MA
背景聚乙二醇脂质体阿霉素具有药理学和安全性优于传统阿霉素。在这项非随机性试验中，192名新诊断的活动性多发性骨髓瘤患者随机接受聚乙二醇脂质体阿霉素联合治疗，（40 mg/m2）和长春新碱1.4mg/m（2）;最大值，第1天静脉输注2.0 mg），第1-4天口服剂量减少的地塞米松（40 mg）（DVd）（n = 97例患者）或联合长春新碱（0.4 mg/天）和常规多柔比星（9 mg/m2/天），在第1-4天连续静脉输注，加上减少剂量的地塞米松（VAd）（n = 95例患者），持续至少4个周期。治疗每4周重复一次，直到患者达到最大反应、疾病进展或不可接受的毒性或接受移植。主要终点是反应和毒性。治疗组间的客观缓解率（Dvd，44%; VAd，41%）、无进展生存期（风险比，1.11; P = 0.69）和总生存期（风险比，0.88; P = 0.67）相似。然而，Dvd与3/4级中性粒细胞减少症或血小板减少性发热（10% vs. 24%; P = 0.01）、败血症发生率较低和抗生素使用较少相关。与VAd相比，Dvd也显著降低了对中心静脉通路（P < 0.0001）和生长因子支持（P = 0.03）的需求，并导致脱发减少（20%比44%; P < 0.001），但手足综合征增加（25%比1%; P < 0.001），主要为1/2级。DVd方案与VAD方案相比，具有相似的疗效，毒性和支持治疗更少，这将提高临床应用并优化移植机会。
BACKGROUND. Pegylated liposomal doxorubicin has pharmacologic and safety advantages over conventional doxorubicin.METHODS. For this noninteriority trial, 192 patients with newly diagnosed, active multiple myeloma were randomized to receive either combined pegylated liposomal doxorubicin (40 mg/m(2)) and vincristine (1.4 mg/m(2); maximum, 2.0 mg) as an intravenous infusion on Day 1 plus reduced-dose dexamethasone (40 mg) orally on Days 1-4 (DVd) (n = 97 patients) or combined vincristine (0.4 mg per day) and conventional doxorubicin (9 mg/m2 per day) as a continuous intravenous infusion on Days 1-4 plus reduced-dose dexamethasone (VAd) (n = 95 patients) for at least 4 cycles.. Treatment was repeated every 4 weeks until patients either achieved maximal response, disease progression, or unacceptable toxicity or underwent transplantation. The primary endpoints were response and toxicity.RESULTS. Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between the treatment groups. However, DVd was associated with significantly less Grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), a lower incidence of sepsis, and less antibiotic use. Compared with VAd, DVd also significantly decreased the need for central venous access (P < 0.0001) and growth-factor support (P = 0.03) and resulted in less alopecia (20% vs. 44%; P < 0.001) but more hand-foot syndrome (25% vs. 1%; P < 0.001), mainly Grade 1/2.CONCLUSIONS. The DVd regimen demonstrated similar efficacy with less toxicity and supportive care compared with VAd, which should improve clinical utility and optimize the opportunity for transplantation.