CLIN CANCER RES:CPI-613联合大剂量阿糖胞苷和米托蒽醌治疗复发或耐药急性髓系白血病

2018-05-09 MedSci MedSci原创

CPI-613可以抑制PDH和α-KGDH,在髓系恶性疾病中具有治疗活性。CLIN CANCER RES近期发表了一篇文章,研究线粒体代谢在化疗反应中的作用并探索CPI-613联合大剂量阿糖胞苷和米托蒽醌治疗复发或耐药急性髓系白血病的最大耐受剂量(MTD),有效性和安全性。

CPI-613可以抑制PDH和α-KGDH,在髓系恶性疾病中具有治疗活性。CLIN CANCER RES近期发表了一篇文章,研究线粒体代谢在化疗反应中的作用并探索CPI-613联合大剂量阿糖胞苷和米托蒽醌治疗复发或耐药急性髓系白血病的最大耐受剂量(MTD),有效性和安全性。

作者在细胞系和动物模型中研究线粒体对化疗的反应。在复发或耐药急性髓系白血病患者中进行CPI-613联合阿糖胞苷和米托蒽醌的Ⅰ期临床试验。研究结果表明,化疗暴露会诱导线粒体PDH依赖的氧摄取。CPI-613使得急性髓系白血病细胞对化疗敏感,表明线粒体代谢是耐药的原因之一。缺少p53不改变对CPI-613的反应。Ⅰ期临床试验纳入67例患者,62例可以评估反应。总反应率为50%。中位生存期为6.7个月。60岁以上的患者CR/CRi率为47%,中位生存期为6.9个月。细胞遗传学风险低的患者反应率达到46%(11/24)。对一些骨髓样本进行基线RNA测序分析发现有治疗反应的患者的一个基因表达特征与治疗前骨髓中B细胞存在相符合。

文章最后认为,化疗联合CPI-613是年龄较大的患者及细胞遗传学风险低的患者的理想治疗方式。

原始出处:
Timothy S.Pardee,Rebecca G.Anderson,et al.A Phase ⅠStudy of CPI-613 in Combination with High-Dose Cytarabine and Mitoxantrone for Relapsed or Refractory Acute Myeloid Leukemia.CLIN CANCER RES.May 2018 doi:10.1158/1078-0432.CCR-17-2282

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    2019-03-06 swallow
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    2018-05-13 zwjnj2

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