Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma
Phase 2 study of arsenic trioxide in patients with relapsed or refractory multiple myeloma
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DOI：
10.1111/j.1365-2141.2004.04941.x
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发表时间：
2004-05-01
影响因子：
6.5
通讯作者：
Ellison, R
中科院分区：
文献类型：
--
作者：
Hussein, MA;Saleh, M;Ellison, R
尽管积极和创新的治疗，患者多发性骨髓瘤（MM）总是复发和死亡的疾病。需要新的非细胞毒性挽救治疗方案和额外的治疗策略。三氧化二砷是一种具有多方面作用机制的抗肿瘤药物，在体外诱导MM细胞系和MM患者新鲜分离的细胞凋亡，并且在初步研究中，在晚期MM患者中显示出临床活性。在24名MM患者中进行了一项多中心、开放标签的二期三氧化二砷研究；8例复发，16例既往治疗难治性。患者在每4周周期的前2周接受三氧化二砷0.25 mg/kg/d，连续5 d/周。16例患者有3级或4级中性粒细胞减少症，1例需要抗生素治疗。24例患者中有8例（33%）血清m蛋白水平降低（25%或更多）。另有6例（25%）患者病情稳定。中位反应时间为67.5天，中位反应持续时间为130天。三氧化二砷治疗降低了两名基线值较高的患者的血清肌酐水平。这些数据表明，三氧化二砷作为单药抢救治疗是有效的，并且耐受性相当好，即使在晚期、复发和难治性MM患者中也是如此。
Despite aggressive and innovative therapy, patients with multiple myeloma (MM) invariably relapse and die of their disease. New options for non-cytotoxic salvage therapy and additional therapeutic strategies are needed. Arsenic trioxide, an antitumour agent with a multifaceted mechanism of action, induces apoptosis in vitro in MM cell lines and freshly isolated cells from MM patients and, in preliminary studies, displayed clinical activity in patients with late-stage MM. A phase 2, multicentre, open-label study of arsenic trioxide was conducted in 24 MM patients; eight had relapsed and 16 were refractory to prior therapy. Patients received arsenic trioxide 0.25 mg/kg/d for 5 d/week during the first 2 weeks of each 4-week cycle. Sixteen patients had grade 3 or 4 neutropenia and one required antibiotics. Reductions (25% or more) in serum M-protein levels occurred in eight of 24 (33%) patients. An additional six (25%) patients had stable disease. The median time to response was 67.5 d, with a median duration of response of 130 d. Arsenic trioxide therapy lowered serum creatinine levels in two patients with high baseline values. These data indicate that arsenic trioxide is active and reasonably well tolerated as a single-agent salvage therapy, even in patients with late-stage, relapsed and refractory MM.