Li Jian-Ri, Chiu Kun-Yuan, Wang Shian-Shiang, Yang Cheng-Kuang, Chen Chuan-Shu, Ho Hao-Chung, Hung Chi-Feng, Cheng Chen-Li, Yang Chi-Rei, Chen Cheng-Che, Wang Shu-Chi, Lin Chia-Yen, Chang Chao-Hsiang, Hsu Chiann-Yi, Ou Yen-Chuan
Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
Institute of Medicine, Chung Sang Medical University, Taichung, Taiwan.
Front Pharmacol. 2017 Nov 22;8:836. doi: 10.3389/fphar.2017.00836. eCollection 2017.
Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic castration resistant prostate cancer. In this study, we attempt to analyze the role of conventional anti-androgen drugs as deferred CAB therapy in castration-resistant prostate cancer patients. From 2012 to 2017, 48 metastatic castration-resistant prostate cancer (CRPC) patients who received sequential treatments with primary androgen blockade, oral anti-androgen regimens, and docetaxel followed by AA treatment were included. We defined effective deferred CAB as any decline of PSA after add-on antiandrogen after CRPC. Patients were separated into effective and ineffective deferred CAB. Comparison between two groups in the first line androgen deprivation therapy duration, CRPC PSA level, pre-AA PSA level, chemotherapy dosages, duration, and patients progression free survival and overall survival after AA treatment were analyzed. Twenty-three patients (47.9%) achieved PSA decline after deferred CAB. Among total 48 patients, 24 patients experienced PSA decline more than 50% after AA treatment. The median PSA progression-free survival and overall survival after AA treatment in the total cohort of 48 patients were 4.4 and 24.3 months, respectively. The effective deferred CAB group showed significantly lower PSA level, lower percentage of PSA progression, higher total follow-up duration, higher percentage of surviving patients, better progression free survival, and overall survival estimate after AA treatment. Of the eight variables analyzed, effectiveness in deferred CAB showed positive association to progression free survival (HR 0.29, 95% CI 0.12-0.67, = 0.004) and overall survival (HR 0.24, 95% CI 0.07-0.81, = 0.022). First line androgen deprivation therapy (ADT) duration also showed positive association to overall survival (HR 0.95, 95% CI 0.91-0.99, = 0.023). Effectiveness of deferred CAB therapy was positively associated with progression free survival and overall survival of AA treatment after docetaxel. It can be used as a pre-treatment predictor.
传统抗雄激素方案曾被广泛用作晚期前列腺癌患者的初始治疗或联合雄激素阻断（CAB）治疗。目前，新型雄激素途径抑制剂如醋酸阿比特龙（AA）和恩杂鲁胺已被证明对转移性去势抵抗性前列腺癌有效。在本研究中，我们试图分析传统抗雄激素药物作为去势抵抗性前列腺癌患者延迟CAB治疗的作用。2012年至2017年，纳入了48例转移性去势抵抗性前列腺癌（CRPC）患者，这些患者接受了序贯治疗，包括初始雄激素阻断、口服抗雄激素方案、多西他赛，随后接受AA治疗。我们将有效的延迟CAB定义为CRPC后加用抗雄激素药物后PSA的任何下降。患者被分为有效的和无效的延迟CAB组。分析了两组在一线雄激素剥夺治疗持续时间、CRPC时的PSA水平、AA治疗前的PSA水平、化疗剂量、持续时间以及患者在AA治疗后的无进展生存期和总生存期的差异。23例患者（47.9%）在延迟CAB后PSA下降。在48例患者中，24例患者在AA治疗后PSA下降超过50%。48例患者的总队列中，AA治疗后的中位PSA无进展生存期和总生存期分别为4.4个月和24.3个月。有效的延迟CAB组显示出显著更低的PSA水平、更低的PSA进展百分比、更长的总随访时间、更高的存活患者百分比、更好的无进展生存期以及AA治疗后的总生存估计。在分析的八个变量中，延迟CAB的有效性与无进展生存期呈正相关（HR 0.29，95%CI 0.12 - 0.67，P = 0.004）和总生存期呈正相关（HR 0.24，95%CI 0.07 - 0.81，P = 0.022）。一线雄激素剥夺治疗（ADT）持续时间也与总生存期呈正相关（HR 0.95，95%CI 0.91 - 0.99，P = 0.023）。延迟CAB治疗的有效性与多西他赛后AA治疗的无进展生存期和总生存期呈正相关。它可作为一种治疗前预测指标。
