Individualized Tamoxifen Dose Escalation-Response.
Individualized Tamoxifen Dose Escalation-Response.
复制标题
个体化他莫昔芬剂量递增反应。
DOI：
10.1158/1078-0432.ccr-16-2351
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Rae,JamesM
中科院分区：
文献类型：
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作者：
Hertz,DanielL;Rae,JamesM
我们感谢Koolen及其同事对我们关于缺乏证据支持基于预测或测量的内昔芬浓度的他莫昔芬剂量递增的评论的周到回应（1）。他们指出，”如果测量的浓度远低于目前采用的有效性最低值约6 ng/mL，我们认为不干预和不试图增加暴露是不道德的。在他们的声明中，关键的短语是“如果浓度已经被测量”，而在我们的评论中，我们采取的立场是，由于目前缺乏证据支持这种方法，不应该测量内昔芬浓度。作者认为，服用他莫昔芬的乳腺癌患者可以从全身内昔芬浓度测量中获益。作为临床药理学家，我们同意药物浓度较低的患者可能会经历较差的治疗效果;然而，生物标志物假设有一个既定的转化途径。两个关键步骤是：（i）确认生物标志物与治疗结果相关（“临床有效性”）和（ii）证明生物标志物收集改善治疗结果（“临床效用”）。目前，有大量的
We thank Koolen and colleagues for their thoughtful response to our commentary about the lack of evidence supporting tamoxifen dose escalation based on predicted or measured endoxifen concentrations (1). They state that" if the concentration has been measured and it is far below the currently adopted minimum value for efficacy of approximately 6 ng/mL, we feel it is unethical not to intervene and not trying to increase the exposure." The critical phrase in their assertion is" if the concentration has been measured," whereas in our commentary, we take the position that endoxifen concentrations should not be measured given the current lack of evidence supporting this approach.The authors posited that breast cancer patients taking tamoxifen could benefit from systemic endoxifen concentration measurements. As clinical pharmacologists, we agree that patients with lower drug concentrations may experience inferior therapeutic effectiveness; however, there is an established translational pathway for biomarker hypotheses. The two critical steps are:(i) confirming that the biomarker is associated with a treatment outcome (" clinical validity") and (ii) demonstrating that biomarker collection improves a treatment outcome (" clinical utility"). Currently, there are a large number of