Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients
Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients
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DOI：
10.1016/j.ejca.2016.11.027
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发表时间：
2017-02-01
影响因子：
8.4
通讯作者：
Alexandre, J.
中科院分区：
文献类型：
--
作者：
Carton, E.;Noe, G.;Alexandre, J.
背景：阿比特龙（ABI）是治疗转移性去势抵抗性前列腺癌（mCRPC）患者的主要口服药物，但其全身暴露量存在较大的个体差异。我们的目的是探讨 mCRPC 患者 ABI 血浆谷浓度与前列腺特异性抗原 (PSA) 反应之间的关系，并确定其活性的关键决定因素。 患者和方法：这是一项针对接受 ABI 治疗的 mCRPC 患者的单中心前瞻性观察研究。使用带有荧光检测的液相色谱法测量稳态时 ABI 的血浆浓度：主要目的是研究平均 ABI 血浆暴露量 (ABI C-min) 与 3 个月 PSA 反应之间的关系。 结果：从 2012 年至 2016 年，61 名 mCRPC 患者符合药代动力学/药效学评估的条件。 38 名患者经历了 PSA 反应（62%，[置信区间 {CI} 95% 50-78]）。在单变量分析中，应答者的 ABI Cmin 高出 1.5 倍：12.0 ng/mL (CI 95% 9.4-15.6) 与 8.0 ng/mL (CI 95% 5.8-11.6；P = 0.0015)。在多变量分析中，只有 ABI Cmin 与 PSA 反应独立相关（比值比 = 1.12 [CI 95% 1.01-1.25]，P = 0.004）。通过接受者操作特征分析，ABI Crain 的最佳阈值是 8.4 ng/mL。 ABI Cinin 高于 8.4 ng/mL 的患者的无进展生存期 (PFS) 显着更高（风险比 0.55，[CI 95% 0.31-0.99]、12.2 [CI 95% 9.2-19.5] 与 7.4 [CI 95% 5.5-14.7] 个月相比。否则，P = 0.044）。结论：我们显示 ABI 谷浓度与 PSA 反应和 PFS 相关。此外，我们可以确定 PSA 反应的血浆浓度截止值。总而言之，ABI 浓度监测似乎是改善 mCPRC 患者临床结果的一种新方法。 (C) 2016 Elsevier Ltd. 保留所有权利。
Background: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity.Patients and methods: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection: The primary objective was to study the relationship between mean ABI plasma exposure (ABI C-min) and 3-month PSA response.Results: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Crain was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cinin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months. otherwise, P = 0.044).Conclusions: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients. (C) 2016 Elsevier Ltd. All rights reserved.