A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid.
A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid.
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DOI：
10.1002/cncr.26517
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发表时间：
2012-05-01
期刊：
影响因子：
6.2
通讯作者：
Qazilbash MH
中科院分区：
文献类型：
--
作者：
Sharma M;Khan H;Thall PF;Orlowski RZ;Bassett RL Jr;Shah N;Bashir Q;Parmar S;Wang M;Shah JJ;Hosing CM;Popat UR;Giralt SA;Champlin RE;Qazilbash MH
硼替佐米对新诊断和复发的多发性骨髓瘤有效，并与美法仑具有协同活性。我们进行了一项随机试验，以确定在三氧化二砷（ATO）、抗坏血酸（AA）和美法仑的预备方案中添加硼替佐米的安全性和有效性。 2006年10月至2007年9月期间入组的60名患者中，58名接受自体移植，准备方案为马法兰200 mg/m2静脉注射、AA 1000 mg/天静脉注射×7天和ATO 0.25 mg/kg静脉注射×7天。患者被随机分为不接受硼替佐米治疗（第 1 组）、硼替佐米 1 mg/m2 × 3 剂量（第 2 组）和硼替佐米 1.5 mg/m2 × 3 剂量（第 3 组）。主要终点是完全缓解 (CR)、4 级毒性和 90 天治疗相关死亡率 (TRM)。次要终点是无进展生存期（PFS）和总生存期（OS）。所有幸存患者的中位随访时间为 36 个月（范围 20-43）。第1、2和3组的CR率分别为20%、10%和10%。 3-4 级非血液学毒性和 TRM 具有可比性。这些组中尚未达到中位 OS，而中位 PFS 分别为 17.8、17.4 和 20.7 个月。无论治疗组如何，具有高风险细胞遗传学（p0.016 和 0.0001）和疾病复发（p=0.0001 和 0.0001）的患者的 PFS 和 OS 均显着缩短。在 ATO、AA 和高剂量美法仑的预备方案中添加硼替佐米对于多发性骨髓瘤患者来说是安全且耐受性良好的。硼替佐米组的 CR 率、PFS 或 OS 没有显着改善。
Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and has synergistic activity with melphalan. We conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA) and melphalan. Among 60 patients enrolled between October 2006 and September 2007, 58 received autologous transplantation with a preparative regimen of melphalan 200 mg/m2 IV, AA 1000 mg/day IV × 7 days and ATO 0.25 mg/kg IV × 7 days. Patients were randomized to receive no bortezomib (group 1), bortezomib 1 mg/m2 × 3 doses (group 2), and bortezomib 1.5 mg/m2 × 3 doses (group 3). Primary endpoints were complete response (CR), grade 4 toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free (PFS) and overall survival (OS). Median follow-up in all surviving patients was 36 months (range 20–43). CR rates in groups 1, 2 and 3 were 20%, 10% and 10%. Grade 3–4 non-hematologic toxicities and TRM were comparable. Median OS has not been reached in the groups, while median PFS was 17.8, 17.4 and 20.7 months, respectively. PFS and OS were significantly shorter in patients with high-risk cytogenetics (p0.016 and 0.0001) and relapsed disease (p=0.0001 and 0.0001) regardless of the treatment group. Adding bortezomib to a preparative regimen of ATO, AA and high dose melphalan is safe and well tolerated in patients with multiple myeloma. There was no significant improvement in CR rate, PFS or OS in the bortezomib groups.
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DOI：
10.3816/clm.2009.n.056
发表时间：
2009-08
期刊：
Clinical lymphoma & myeloma
影响因子：
--
作者：
Kyle RA;Rajkumar SV
通讯作者：
Rajkumar SV
影响因子：
6.2
作者：
Anagnostopoulos, A;Aleman, A;Giralt, S
通讯作者：
Giralt, S
影响因子：
--
作者：
Fisher, RA
通讯作者：
Fisher, RA
影响因子：
11.4
作者：
Durie, B. G. M.;Harousseau, J-L;Rajkumar, S. V.
通讯作者：
Rajkumar, S. V.
影响因子：
20.3
作者：
Mitsiades, N;Mitsiades, CS;Anderson, KC
通讯作者：
Anderson, KC