Arsenic trioxide in patients with myelodysplastic syndromes: A phase II multicenter study
Arsenic trioxide in patients with myelodysplastic syndromes: A phase II multicenter study
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DOI：
10.1200/jco.2005.03.9503
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发表时间：
2006-06-01
影响因子：
45.3
通讯作者：
Fenaux, P
中科院分区：
文献类型：
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作者：
Vey, N;Bosly, A;Fenaux, P
目的评价三氧化二砷治疗骨髓增生异常综合征（MDS）患者的安全性和有效性。方法根据法国、美国和英国标准诊断的MDS患者接受三氧化二砷负荷剂量0.3mg/kg/d，连续5d，随后维持剂量0.25mg/kg，每周2次，连续15周。患者被分为两个队列：低风险MDS（国际预后评分系统风险类别低或中等1）和高风险MDS（国际预后评分系统风险类别中等2或高）。修改后的国际工作组标准用于响应evaluation.Results的115例患者入组和治疗的研究，67%的患者在基线输血依赖，中位年龄为68岁。大多数治疗相关不良事件为轻度至中度。血液学改善（意向治疗）的总体发生率为24/115（19%），包括高风险队列中的1例完全缓解和1例部分缓解。血液学缓解率在低危和高危MDS患者中分别为13/50（26%）和11/64（17%）。在所有三种血液学谱系中均观察到主要反应; 16%的RBC输注依赖性患者和29%的血小板输注依赖性患者变得不依赖于输血。在数据截止时，中位反应持续时间为3.4个月，与反应正在进行中的9 patient.Conclusion三氧化二砷治疗组成的初始负荷剂量，然后维持治疗MDS中有中度活动，诱导血液学反应的低风险和高风险的患者。这种活性加上可控制的不良反应特征，保证了三氧化二砷治疗MDS患者的额外研究，特别是在联合治疗中。
Purpose Evaluation of the safety and efficacy of arsenic trioxide in patients with myelodysplastic syndromes (MDS).Patients and Methods MDS patients diagnosed according to standard French-American-British criteria received a loading dose of 0.3 mg/kg per day of arsenic trioxide for 5 days followed by a maintenance dose of 0.25 mg/kg arsenic trioxide twice weekly for 15 weeks. Patients were divided into two cohorts: lower-risk MDS (International Prognostic Scoring System risk category low or intermediate 1) and higher-risk MDS (International Prognostic Scoring System risk category intermediate 2 or high). Modified International Working Group criteria were used for response evaluation.Results Of 115 patients enrolled and treated in the study, 67% of patients were transfusion dependent at baseline; median age was 68 years. Most treatment-related adverse events were mild to moderate. The overall rate of hematologic improvement (intent-to-treat) was 24 (19%) of 115, including one complete and one partial response in the higher-risk cohort. The hematologic response rates were 13 (26%) of 50 and 11 (17%) of 64 in patients with lower-risk and higher-risk MDS, respectively. Major responses were observed in all three hematologic lineages; 16% of RBC transfusion-dependent patients and 29% of platelet transfusion-dependent patients became transfusion independent. At data cut off, the median response duration was 3.4 months, with responses ongoing in nine patients.Conclusion Arsenic trioxide treatment consisting of an initial loading dose followed by maintenance therapy has moderate activity in MDS, inducing hematologic responses in both lower- and higher-risk patients. This activity combined with a manageable adverse effect profile warrants the additional study of arsenic trioxide, particularly in combination therapy, for the treatment of patients with MDS.