促性腺激素释放激素拮抗剂治疗前列腺癌后游离前列腺特异性抗原或人激肽释放酶相关肽 2 的快速消除动力学：快速监测治疗反应的潜力。

Rapid elimination kinetics of free PSA or human kallikrein-related peptidase 2 after initiation of gonadotropin-releasing hormone-antagonist treatment of prostate cancer: potential for rapid monitoring of treatment responses.

机构信息

Department of Urology, Lund University, Skåne University Hospital, Malmö, Sweden.

出版信息

Clin Chem Lab Med. 2012 Nov;50(11):1993-8. doi: 10.1515/cclm-2011-0967.

DOI:10.1515/cclm-2011-0967

PMID:22718641

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3474140/

Abstract

BACKGROUND

The utility of conventional prostate-specific antigen (PSA) measurements in blood for monitoring rapid responses to treatment for prostate cancer is limited because of its slow elimination rate. Prior studies have shown that free PSA (fPSA), intact PSA (iPSA) and human kallikrein-related peptidase 2 (hK2) are eliminated more rapidly after radical prostatectomy. In contrast, all three markers have similarly slow elimination rates after castration induced by gonadotropin-releasing hormone (GnRH) agonists, possibly due to the slow onset of castration. Therefore, we assessed elimination rates of tPSA, fPSA, iPSA and hK2 after rapid induction of castration with degarelix (Firmagon(®)), a novel GnRH antagonist.

METHODS

This study included 24 patients treated with degarelix. Blood was taken at 1, 3, 7, 14, 21 and 28 days after injection of degarelix. Free and total PSA were measured with a commercial dual-label assay, and with inhouse research assays of intact PSA and hK2.

RESULTS

Median (interquartile range, IQR) tPSA at baseline was 23.4 (15.8, 59.8). Twenty-two patients (92 % ) reached castrate levels of testosterone within 24 h of degarelix initiation, and all patients did so within 72 h. All kallikrein forms declined in an exponential fashion after degarelix administration. The median time to 50 % reduction in biomarker level was 8 – 9 days for tPSA or complexed PSA vs. 2-4 days for hK2, iPSA and fPSA. The percentage eliminated at day 3 and day 7 was significantly higher for hK2, iPSA and fPSA than for tPSA (all p < 0.02), while tPSA and complexed PSA were similar.

CONCLUSIONS

The rapid decline of fPSA, iPSA and hK2 after fast induction of castration with degarelix is similar to that reported after prostatectomy and offers a novel, informative method to monitor rapid onset of therapeutic action targeting signaling of the androgen receptor.

摘要

背景

传统的前列腺特异性抗原（PSA）在血液中的检测在监测前列腺癌治疗的快速反应方面的作用有限，因为其消除率较慢。先前的研究表明，游离前列腺特异性抗原（fPSA）、完整 PSA（iPSA）和人激肽释放酶相关肽 2（hK2）在根治性前列腺切除术后消除更快。相比之下，在促性腺激素释放激素（GnRH）激动剂诱导去势后，所有这三种标志物的消除率都同样缓慢，这可能是由于去势的缓慢发生。因此，我们评估了使用新型 GnRH 拮抗剂 degarelix（Firmagon(®)）快速诱导去势后 tPSA、fPSA、iPSA 和 hK2 的消除率。

方法

本研究纳入了 24 例接受 degarelix 治疗的患者。degarelix 注射后 1、3、7、14、21 和 28 天采集血液。使用商业双标记测定法和内研的完整 PSA 和 hK2 检测法测量游离和总 PSA。

结果

基线时中位（四分位距，IQR）tPSA 为 23.4（15.8，59.8）。22 例患者（92%）在 degarelix 起始后 24 小时内达到去势水平的睾酮，所有患者在 72 小时内达到这一水平。所有激肽形式在 degarelix 给药后呈指数下降。生物标志物水平降低 50%的中位时间为 tPSA 或复合 PSA 为 8-9 天，而 hK2、iPSA 和 fPSA 为 2-4 天。degarelix 给药后第 3 天和第 7 天，hK2、iPSA 和 fPSA 的消除率明显高于 tPSA（均 p<0.02），而 tPSA 和复合 PSA 则相似。