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作为转移性黑色素瘤的治疗点的KIT
Richard D Carvajal1, Cristina R Antonescu, Jedd D Wolchok
1Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. carvajar@mskcc.org
JAMA
|June 7, 2011
概括
伊马替尼甲酸在患有晚期黑色素瘤且含有KIT变化的患者中显示出临床反应. 在具有功能相关KIT改变的瘤中,反应的可能性更高.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 一些黑色素瘤,特别是来自,粘膜和阳光损伤部位的黑色素瘤,表现出KIT受体氨酸激酶的激活突变和放大.
- 这项研究研究了使用伊马替尼甲酸在这种特定的黑色素瘤分子子集中抑制KIT的治疗潜力.
研究的目的:
- 为了评估伊马替尼甲酸的临床疗效,在被诊断为患有黑色素瘤的患者中,怀有KIT变化.
- 评估特定分子变化与对伊马替尼甲酸治疗的临床反应之间的相关性.
主要方法:
- 一个2期,开放标签,单组试验,涉及28名患有晚期不可切除黑色素瘤的患者,并确定了KIT突变或放大.
- 患者每天两次服用400毫克口服剂量的伊马替尼布梅西酸盐.
- 主要终点是放射性反应,次要终点包括进展时间和整体存活率.
主要成果:
- 在25名可评估患者中,观察到16%的持久反应率 (2个完整反应,2个持久的部分反应).
- 病情进展的中位时间为12周,平均整体存活时间为46.3周.
- 在瘤中发现了更高的响应率 (40%),这些瘤在重复的热点中发生了突变,或者突变对野生类型等位基因比率很高,这表明积极选择.
结论:
- 伊马替尼西酸盐在KIT改变的晚期黑色素瘤患者的一个子集中表现出显著的临床活性.
- 临床反应似乎与已证明具有功能重要性的KIT变化有关.
- 这些发现支持针对具有特定KIT变化的黑色素瘤的向治疗.
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