Mori Keiichiro, Kimura Takahiro, Onuma Hajime, Kimura Shoji, Yamamoto Toshihiro, Sasaki Hiroshi, Miki Jun, Miki Kenta, Egawa Shin
Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
Prostate. 2017 Jul;77(10):1144-1150. doi: 10.1002/pros.23373. Epub 2017 May 30.
An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone.
This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model.
Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05).
The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS.
去势抵抗性前列腺癌（CRPC）仍有一系列临床问题有待解决，包括用药顺序和药物交叉耐药性。目前，对于雄激素受体轴靶向（ARAT）药物，特别是恩杂鲁胺和阿比特龙等新型药物的最佳使用顺序，尚无明确的指南。
本研究回顾性分析了69例接受恩杂鲁胺序贯阿比特龙或反之治疗的CRPC患者。主要结局指标是包括有症状和/或影像学无进展生存期（PFS）的比较性联合无进展生存期。还比较了患者的总前列腺特异性抗原（PSA）-PFS、总生存期（OS）和PSA反应。采用向后逐步多变量Cox模型分析联合PFS和OS的预测因素。
69例患者中，46例先接受恩杂鲁胺治疗，随后接受阿比特龙治疗（E-A组），23例先接受阿比特龙治疗，随后接受恩杂鲁胺治疗（A-E组）。除血红蛋白值外，两组的基本数据无显著差异。在Kaplan-Meier分析中，与E-A组相比，A-E组显示出更好的联合PFS（P = 0.043）。总PSA-PFS也得到了类似结果（P = 0.049），而两组间OS无差异（P = 0.62）。多变量分析表明，治疗前乳酸脱氢酶（LDH）值和年龄是联合PFS较长的显著预测因素（P < 0.05）。同样，多变量分析表明，治疗前血红蛋白值和体能状态是OS较长的显著预测因素（P < 0.05）。
本研究结果表明，在CRPC患者中，与E-A顺序相比，A-E顺序的联合PSA和总PSA-PFS更长。序贯治疗中的LDH值可能作为联合PFS较长的预测指标。
