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当代肿瘤药物靶点

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ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

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Clinical Trial

Selinexor (KPT-330)，一种口服选择性核出口抑制剂(SINE)化合物，联合FOLFOX用于转移性结直肠癌(mCRC)患者——I期临床试验的最终结果

卷 20, 期 10, 2020

页: [811 - 817] 页: 7

弟呕挨: 10.2174/1568009620666200628105727

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摘要

背景：Selinexor是一种口服核出口化合物选择性抑制剂，特异性阻断染色体区域维持蛋白1。 目的：评价逐步加大剂量selinexor联合5-氟尿嘧啶、亚叶酸钙和奥沙利铂(mFOLFOX6)治疗转移性结直肠癌(mCRC)患者的安全性和耐受性。 方法：在这项多中心I期试验中，符合以奥沙利铂为基础的治疗方案的mCRC患者，被纳入每两周的第1、3、8天接受一次口服selinexor 联用mFOLFOX6治疗。主要终点为最大耐受剂量。次要终点为毒性、总有效率、无进展生存期和总生存期。 结果：共有10名患者入选，他们之前接受过奥沙利铂(6/10)、伊立替康(8/10)、贝伐珠单抗(6/10)或抗EGFR治疗(5/10)。连续4名患者接受40 mg selinexor联用mFOLFOX6治疗剂量。所有四名患者都经历了剂量限制毒性，并在中位两个周期后退出研究。因此，这个剂量水平被认为是有毒的，没有进一步的患者评估在这个剂量。6名患者以20mg selinexor联用mFOLFOX6治疗剂量入组。尽管耐受性较好，4名患者在第一个周期后退出(患者意愿)，只有2名患者继续到疾病进展。最常见报道的治疗不良事件为恶心(80%)、腹泻(70%)、呕吐(60%)、疲劳(60%)、厌食(40%)和视力受损(40%)。由于治疗暴露时间较短，未观察到相关临床活动。 结论：在转移性结直肠癌患者中，selinexor联用mFOLFOX6是不可耐受的。可以评估其他给药方案或组合。临床试验标识NCT02384850。

关键词: 转移性结直肠癌，结直肠癌，mCRC

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