多西他赛治疗期间去势抵抗性前列腺癌患者神经介质动力学的前瞻性评估

Prospective Evaluation of Neuromediator Dynamics in Castration-Resistant Prostate Cancer Patients During Docetaxel.

作者信息

VON Hardenberg Jost, Schwartz Maike, Werner Thorsten, Fuxius Stefan, Müller Markus, Frangenheim Thomas, Bolenz Christian, Weiss Christel, Heinrich Elmar

机构信息

Department of Urology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.

Outpatient Urology Practice, Herzberg am Harz, Germany.

出版信息

Anticancer Res. 2017 Sep;37(9):5117-5124. doi: 10.21873/anticanres.11931.

DOI:10.21873/anticanres.11931

PMID:28870943

Abstract

AIM

Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy.

PATIENTS AND METHODS

A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points. Outcome measures were overall survival (OS), progression-free survival (PFS) and PSA nadir.

RESULTS

Fifty-two patients were included. A general rise in CGA levels was observed. Patients with a high CGA rise (100%ULN: CGA ≥98.1ng/ml) between the 1st and 3rd cycle trended towards a decreased OS (p=0.0649) and showed a decreased PFS (p=0.0369). In multivariate analysis, continuous CGA rise correlated with PFS (p=0.0553; HR 1.136), but was not an independent predictor of OS.

CONCLUSION

Patients with an early high CGA rise may demonstrate a subgroup with poor outcome due to underlying SCNC transformation. Monitoring of CGA appears to be an option worth considering.

摘要

目的

本研究的目的是检测转移性去势抵抗性前列腺癌（mCRPC）中的小细胞/神经内分泌（SCNC）转化，这是一个具有挑战性的过程。我们研究了神经介质动力学作为接受多西他赛治疗患者中SCNC潜在证据的作用。

患者与方法

进行了一项多机构前瞻性观察研究。纳入接受多西他赛治疗的患者。在预定时间点依次评估嗜铬粒蛋白A（CGA）、神经元特异性烯醇化酶（NSE）和胃泌素释放肽前体（Pro-GRP）。观察指标为总生存期（OS）、无进展生存期（PFS）和前列腺特异抗原最低点（PSA nadir）。

结果

纳入52例患者。观察到CGA水平普遍升高。在第1周期和第3周期之间CGA升高幅度大（100%ULN：CGA≥98.1ng/ml）的患者总生存期有降低趋势（p=0.0649），无进展生存期降低（p=0.0369）。在多变量分析中，CGA持续升高与无进展生存期相关（p=0.0553；HR 1.136），但不是总生存期的独立预测因素。