Arsenic trioxide-based therapy in relapsed/refractory multiple myeloma patients: a meta-analysis and systematic review.
Arsenic trioxide-based therapy in relapsed/refractory multiple myeloma patients: a meta-analysis and systematic review.
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DOI：
10.2147/ott.s67165
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发表时间：
2014
影响因子：
4
通讯作者：
Chen H
中科院分区：
文献类型：
--
作者：
He X;Yang K;Chen P;Liu B;Zhang Y;Wang F;Guo Z;Liu X;Lou J;Chen H
多发性骨髓瘤（MM）是一种克隆性恶性肿瘤，其特征是骨髓中恶性浆细胞的增殖和单克隆免疫球蛋白的产生。尽管一些新批准的药物（沙利度胺、来那度胺和硼替佐米）对多发性骨髓瘤患者显示出显着的益处，改善了生存率，但所有多发性骨髓瘤患者仍然会复发。三氧化二砷（ATO）是治疗急性早幼粒细胞白血病最活跃的单一药物，其抗肿瘤活性部分依赖于活性氧的产生。由于观察到其对 MM 细胞系和原发性骨髓瘤细胞的多方面影响，已在经过大量预处理的复发或难治性 MM 患者中进行了 I/II 期试验。治疗方案在 ATO 剂量和单一疗法与与其他可用于治疗 MM 的药物的联合疗法方面存在显着差异。尽管大多数患者对基于 ATO 的联合治疗耐受性良好，但大多数试验发现 ATO 对 MM 患者的效果有限。然而，由于少数患者被随机分配到不同的治疗组，因此试验尚未具有统计学意义来确定实验组之间无进展生存期和总生存期的差异。因此，需要对基于 ATO 的随机对照试验进行大型 III 期研究，以确定 ATO 在临床环境中是否具有任何潜在的有益作用。
Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with other agents available for the treatment of MM. Although ATO-based combination treatment was well tolerated by most patients, most trials found that ATO has limited effects on MM patients. However, since small numbers of patients were randomized to different treatment arms, trials have not been statistically powered to determine the differences in progression-free survival and overall survival among the experimental arms. Therefore, large Phase III studies of ATO-based randomized controlled trials will be needed to establish whether ATO has any potential beneficial effects in the clinical setting.