系统的安全性和毒性评价fingolimod的潜在使用治疗急性髓系白血病。

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D 'Crus Enjeti AK,梅尔维尔K, Verrills NM,罗林们P

系统的安全性和毒性评价fingolimod的潜在使用治疗急性髓系白血病。

抗癌药物,2016年7月27日(6):560 - 8。doi: 10.1097 / CAD.0000000000000358。

PubMed ID

26967515 (在PubMed

]

文摘

治疗急性髓系白血病(AML)是具有挑战性的和新兴的治疗方案包括蛋白磷酸酶2 (PP2A)活化剂。Fingolimod是已知PP2A激活抑制多个信号通路和营销已被广泛用于多发性硬化症患者和其他迹象。最初的积极成果PP2A活化剂体外和AML承诺的小鼠模型;然而,它的安全使用AML没有评估。从人类研究fingolimod的其他迹象,可以评估是否安全和毒性的PP2A活化剂在治疗AML将允许他们使用。进行了文献回顾,评估安全第一阶段试验开始前PP2A活化剂在AML Fingolimod。从人类研究fingolimod的其他迹象,可以评估是否安全和毒性的PP2A活化剂在治疗AML将允许他们使用。系统综述的文献发表在Medline、EMBASE和Cochrane图书馆进行了批判性的评论。国际标准的设计和报告之后搜索策略。搜索词和医学主题词用于试验涉及PP2A活化剂以及特定的搜索进行“不良事件”,“严重不良事件”,“延迟治疗”,“副作用”和“毒性”为主要目标。 Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is little evidence to suggest specific bone marrow toxicity. Lymophopenia is a desired effect in the management of multiple sclerosis, but may have implications in patients with acute leukaemia as it may potentially increase susceptibility to viral infections such as influenza. Fingolimod is a potential treatment option for AML with an acceptable risk to benefit ratio, given its lack of bone marrow toxicity and the relatively low rate of serious side effects. As most patients with AML are elderly, specific monitoring for cardiac toxicity as well as infection would be required.

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药物

Fingolimod