Rodriguez-Vida Alejo, Bianchini Diletta, Van Hemelrijck Mieke, Hughes Simon, Malik Zafar, Powles Thomas, Bahl Amit, Rudman Sarah, Payne Heather, de Bono Johann, Chowdhury Simon
Guy's and St Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
BJU Int. 2015 Mar;115(3):373-80. doi: 10.1111/bju.12826. Epub 2014 Oct 24.
To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.
We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on-treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.
The median (range) patient age was 70.5 (56-86) years and the median (range) follow-up was 9.0 (0.5-16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.
This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.
在恩杂鲁胺停药后检测前列腺特异性抗原（PSA）水平，以评估恩杂鲁胺是否会引发抗雄激素撤药综合征（AAWS）。
我们回顾性纳入了30例连续的转移性前列腺癌患者，这些患者在多西他赛后接受了恩杂鲁胺治疗。所有患者均有停药后的PSA结果，且在开始进一步的抗癌全身治疗前，每隔2周测定一次。PSA撤药反应定义为PSA较末次治疗时的PSA下降≥50%，且在≥3周后确认下降。使用单因素逻辑回归分析评估患者特征与AAWS的关系。
患者年龄中位数（范围）为70.5（56 - 86）岁，随访中位数（范围）为9.0（0.5 - 16）个月。最常见的转移部位是骨（86.7%）和淋巴结（66.7%）。大多数患者（70%）曾接受过阿比特龙治疗，12例患者（40%）还接受过卡巴他赛治疗。恩杂鲁胺治疗的中位（范围）持续时间为3.68（1.12 - 21.39）个月。恩杂鲁胺停药后监测PSA水平的中位（范围）时间为35（10 - 120）天。恩杂鲁胺停药后，只有1例患者（3.3%）确认PSA反应≥50%。1例患者（3.3%）确认PSA反应在30%至50%之间，另1例患者（3.3%）未经确认的PSA反应在30%至50%之间。总生存期中位数为15.5个月（95%CI 8.1 - 24.7）。单因素分析中所分析的因素均不是恩杂鲁胺停药后PSA下降的显著预测因素。
这项回顾性研究首次提供了证据，表明恩杂鲁胺可能在少数转移性去势抵抗性前列腺癌患者中引发AAWS。需要进一步研究来证实恩杂鲁胺AAWS的存在，并评估其在前列腺癌管理中的相关性。
