JCO:tamoxifen的药物遗传学与代谢

2019-01-27 MedSci MedSci原创

tamoxifen被广泛用作早期乳腺癌患者的辅助治疗。有推测认为endoxifen(他莫昔芬的活性代谢物)的浓度比CYP2D6基因型更能预测他莫昔芬的疗效。在一项回顾性研究中,endoxifen的疗效阈值确定为5.9 ng / mL,但缺乏前瞻性研究的确认。JCO近期发表了一篇文章,研究endoxifen浓度和CYP2D6基因型与接受tamoxifen治疗的早期乳腺癌患者的临床结局之间的联系。

tamoxifen被广泛用作早期乳腺癌患者的辅助治疗。有推测认为endoxifen(他莫昔芬的活性代谢物)的浓度比CYP2D6基因型更能预测他莫昔芬的疗效。在一项回顾性研究中,endoxifen的疗效阈值确定为5.9 ng / mL,但缺乏前瞻性研究的确认。JCO近期发表了一篇文章,研究endoxifen浓度和CYP2D6基因型与接受tamoxifen治疗的早期乳腺癌患者的临床结局之间的联系。

2008年2月至2010年12月,研究纳入接受tamoxifen辅助治疗的乳腺癌患者。收集血液样本检测CYP2D6基因分型和endoxifen浓度。endoxifen浓度作为连续变量进行分析。利用Cox回归模型分析endoxifen浓度和CYP2D6基因型与无复发生存期的关系。研究最终纳入667名绝经前和绝经后患者,入组前接受tamoxifen治疗的中位时间为0.37年。endoxifen浓度和无复发生存之间未发现相关性。此外,使用5.9 ng / mL作为阈值也未改变这些结果。CYP2D6基因型与无复发生存之间也未发现相关性。

文章最后认为,这项前瞻性临床研究表明,接受辅助tamoxifen治疗的早期乳腺癌患者的endoxifen浓度或CYP2D6基因型与临床结局无关。

原始出处:

Anabel Sanchez-Spitman, Vincent Dezentjé et al. Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study. JCO. January 2019 doi: 10.1200/JCO.18.00307

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    2019-01-29 lidong40
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