2期临床试验的deforolimus (AP23573, mk - 8669),一个新颖的哺乳动物雷帕霉素靶抑制剂,在复发或难治性患者血液恶性肿瘤。

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Rizzieri哒,费尔德曼E, Dipersio摩根富林明,Gabrail N,股票W,中国中药R,里维拉VM, Albitar M, Bedrosian CL,贾尔斯陆地

2期临床试验的deforolimus (AP23573, mk - 8669),一个新颖的哺乳动物雷帕霉素靶抑制剂,在复发或难治性患者血液恶性肿瘤。

癌症研究杂志2008年5月1日,14日(9):2756 - 62。doi: 10.1158 / 1078 - 0432. - ccr - 07 - 1372。

PubMed ID

18451242 (在PubMed

]

文摘

目的:Deforolimus (AP23573),小说non-prodrug雷帕霉素类似物,抑制哺乳动物雷帕霉素靶,下游效应器的磷脂酰肌醇3-kinase / Akt和nutrient-sensing通路。第二阶段的试验是确定的疗效和安全性进行单deforolimus复发或难治性患者血液恶性肿瘤。实验设计:符合条件的病人分配到五个特定疾病之一,平行组和每天摄入12.5毫克deforolimus作为一次30分钟的输液5天每2周。西蒙两阶段设计用于每个队列。安全、药物动力学、药效学和抗肿瘤反应进行评估。结果:55例收到deforolimus如下:队列1 23急性骨髓性白血病,两个骨髓增生异常综合征和慢性粒细胞性白血病在nonlymphoid爆炸阶段;队列2中,一个急性淋巴细胞性白血病;组3,九个原因不明的骨髓化生;组4、8慢性淋巴细胞白血病;组5、9套细胞淋巴瘤和两个t细胞白血病/淋巴瘤。 Most patients were heavily pretreated. Of the 52 evaluable patients, partial responses were noted in five (10%), two of seven agnogenic myeloid metaplasia and three of nine mantle cell lymphoma. Hematologic improvement/stable disease was observed in 21 (40%). Common treatment-related adverse events, which were generally mild and reversible, were mouth sores, fatigue, nausea, and thrombocytopenia. Decreased levels of phosphorylated 4E-BP1 in 9 of 11 acute myelogenous leukemia/myelodysplastic syndrome patients after therapy showed mammalian target of rapamycin inhibition by deforolimus. CONCLUSIONS: Deforolimus was well-tolerated in patients with heavily pretreated hematologic malignancies, and antitumor activity was observed. Further investigation of deforolimus alone and in combination with other therapeutic agents is warranted in patients with selected hematologic malignancies.

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药物

Ridaforolimus