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JAMA Oncol:达沙替尼治疗晚期胃肠道间质瘤效果如何?

2018-07-17 吴星 环球医学

2018年6月,发表于《JAMA Oncol》上的一项研究,考察了伊马替尼耐药的晚期胃肠道间质瘤(GIST)患者无进展生存率与达沙替尼的相关性。

2018年6月,发表于《JAMA Oncol》上的一项研究,考察了伊马替尼耐药的晚期胃肠道间质瘤(GIST)患者无进展生存率与达沙替尼的相关性。

重要性:当转移或不适合手术切除时,GIST是威胁生命的。在很少的甲磺酸伊马替尼难治的晚期GIST患者中,苹果酸舒尼替尼后瑞戈非尼治疗可控制肿瘤,但多数患者需要额外的积极治疗。

目的:旨在评估达沙替尼治疗的GIST患者的6个月无进展生存率(PFS)、肿瘤客观应答率和总生存率。

设计、地点和参与者:这项单组临床试验使用贝叶斯设计纳入了13岁或以上的可测量的伊马替尼难治的转移GIST患者,这些患者于2008年6月1日~2009年12月31日在14个肉瘤转诊中心接受治疗。未纳入对照组。患者从入组之日起最短随访5年的生存率。第一个24周期间,每8周使用计算机断层扫描或磁共振成像进行肿瘤影像学检查,此后每12周进行一次。使用Choi标准评估局部部位的肿瘤应答。治疗持续到肿瘤进展、药物剂量降低后出现不可接受的毒性反应、患者或医生的决定。肿瘤组织用于评估原癌基因酪氨酸蛋白激酶Src(SRC)、磷酸化SRC(pSRC)和琥珀酸脱氢酶复合物铁硫亚单位B(SDHB)蛋白的表达,以及酪氨酸激酶受体KIT和血小板源性生长因子受体α多肽(PDGFRA)基因突变。2017年5月19日进行数据分析,2017年12月20日完成。

干预:达沙替尼70mg,口服,每天两次。

主要结局和测量指标:首要终点为6个月PFS,通过高于30%作为阳性药物的证据和低于10%作为不积极治疗的证据进行评估。

结果:本研究中,纳入了50名患者(中位60岁,年龄范围为19~78岁,男性31人(62%),女性19人(38%),白人41人(82%)),其中48人可评估其反应。总体人群中,评估的6个月PFS为29%,14名GIST患者中50%有pSRC。25%患者发生客观肿瘤应答,包括1名PDGFRA18外显子处伊马替尼耐药突变的患者。

结论和意义:达沙替尼在伊马替尼难治的GIST患者中具有活性。需要进一步的研究确定pSRC是否是一个预后生物标志物。

原始出处:

Schuetze SM, Bolejack V, Thomas DG, et.al. Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib. JAMA Oncol. 2018 Jun 1;4(6):814-820. doi: 10.1001/jamaoncol.2018.0601.

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    2018-11-14 minlingfeng
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    2018-07-17 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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    2018-07-17 131****1460

    学习了受益匪浅

    0

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慢性粒细胞白血病慢性期(CML-CP)儿童患者需要有效安全的治疗方案。达沙替尼获得批准用于治疗CML-CP成人和儿童患者。一项Ⅰ期试验确定了费城染色体阳性(Ph+)儿童白血病患者适宜的剂量。CA180-226/NCT00777036是一项Ⅱ期临床试验,纳入<18岁的接受达沙替尼治疗的患者。JCO近期发表了一篇文章,报道了该试验的结果。

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背景:既往的研究通过随机试验发现,相比较于伊马替尼,达沙替尼和尼洛替尼都可用于慢性粒细胞白血病的慢性期(CML-CP)的一线治疗。然而,没有头对头研究直接比较尼洛替尼和达沙替尼治疗新诊断的CML-CP的效果。方法:研究人员通过倾向得分匹配法对接受达沙替尼(n = 102)或尼洛替尼(n = 104)一线治疗CML-CP患者进行了一项2期平行临床试验。结果:通过每个试验相匹配的预处理特性,倾向匹配的

Cancer:达沙替尼治疗CML:减量/停药时代是否已来临?

慢性髓性白血病(CML)已发展成一种由酪氨酸激酶抑制剂(TKI)长期控制的慢性疾病,患者获得长生存后,其治疗重点也转移至药物剂量优化问题,从而在维持治疗效果的同时减少不良反应,并降低经济负担。本综述总结了近期临床试验数据,提示更进一步优化剂量可能可以在减少副作用的同时维持药物的有效性。

溶血药物在逆转衰老细胞损伤方面取得了成功

美国国立卫生研究院资助的一项研究表明,溶血药物的组合可以成功地逆转小鼠的细胞衰老,为未来与年龄相关的抗衰老治疗研究提供了潜在途径

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