TG101348的安全性和有效性,选择性JAK2抑制剂,骨髓纤维化。

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杰米逊Pardanani Gotlib JR, C,科尔特斯我,Talpaz M,石头RM,西尔弗曼MH, Gilliland DG, Shorr J, Tefferi

TG101348的安全性和有效性,选择性JAK2抑制剂,骨髓纤维化。

肿瘤防治杂志。2011年3月1;(7):789 - 96。doi: 10.1200 / JCO.2010.32.8021。Epub 2011 1月10。

PubMed ID

21220608 (在PubMed

]

文摘

目的:骨髓纤维化是一种骨髓恶性肿瘤与贫血、脾肿大,宪法的症状。患者经常港JAK-STAT激活突变对TG101348敏感,选择性小分子Janus激酶2 (JAK2抑制剂)。患者和方法:多中心一期试验,口服TG101348每天服用一次患者高——或者中度风险主要或post-polycythemia维拉/基本血小板增多骨髓纤维化。结果:59例患者治疗,包括28个剂量递增阶段。最大耐受剂量680毫克/天,dose-limiting毒性是可逆的,无症状增加血清淀粉酶水平。继续治疗43例(73%)超过6个周期;累积接触TG101348中值为380天。不良反应包括恶心、呕吐、腹泻、贫血,血小板减少;相应等级3到4发病率分别为3%,3%,10%,35%,24%。TG101348治疗对血清细胞因子水平的影响不大,但是超过半数的患者早期的饱腹感,盗汗,疲劳,瘙痒,咳嗽实现快速和持久的改善这些症状。 By six and 12 cycles of treatment, 39% and 47% of patients, respectively, had achieved a spleen response per International Working Group criteria. The majority of patients with leukocytosis or thrombocytosis at baseline (n = 28 and n = 10, respectively) achieved normalization of blood counts after six (57% and 90%, respectively) and 12 (56% and 88%, respectively) cycles. A significant decrease in JAK2 V617F allele burden was observed at 6 months in mutation-positive patients (n = 51; P = .04), particularly in the subgroup with allele burden greater than 20% (n = 23; P < .01); the decrease was durable at 12 months. CONCLUSION: TG101348 is well tolerated and produces significant reduction in disease burden and durable clinical benefit in patients with myelofibrosis.

DrugBank数据引用了这篇文章

药物

Fedratinib

药物靶点

药物	目标	类	生物	药理作用	行动
Fedratinib	酪氨酸受体激酶JAK2	蛋白质	人类	是的	抑制剂	细节