Poole Austin, Gill David, Hahn Andrew W, Johnson Eric, Carroll Emma, Boucher Kenneth, Nussenzveig Roberto, Maughan Benjamin, Agarwal Neeraj
Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
Clin Genitourin Cancer. 2017 Sep 6. doi: 10.1016/j.clgc.2017.08.017.
Antiandrogen withdrawal syndrome (AAWS), manifested as a prostate-specific antigen (PSA) decline after discontinuation of a first-generation antiandrogen has been well characterized. The objective of the present study was to assess the incidence of AAWS with enzalutamide in men with metastatic castration-resistant prostate cancer.
Patients from a single-institution cohort with metastatic castration-resistant prostate cancer who had discontinued enzalutamide after PSA or radiographic progression were included. AAWS after enzalutamide was defined as any PSA decline after discontinuation of enzalutamide. The baseline patient, disease, and treatment characteristics were compared between patients with and without AAWS after enzalutamide. Statistical analysis of the baseline characteristics included descriptive statistics using the Wilcoxon rank sum test and the Fisher exact test. The median duration of enzalutamide therapy was compared using the log-rank test, and the progression-free survival of the patients with AAWS was evaluated using the Kaplan-Meier method.
Of 47 eligible patients, 5 experienced AAWS after enzalutamide discontinuation. The PSA response in these 5 patients was 84%, 32%, 17%, 15%, and 15%. The median AAWS response time until subsequent PSA progression was 3.3 months. No patient, disease, or treatment characteristics differed among the patients with and without AAWS after enzalutamide discontinuation.
To the best of our knowledge, this is the largest reported cohort documenting the incidence and characterization of AAWS after enzalutamide to date. The AAWS frequency after enzalutamide was low and of short duration. No patient- or disease-related characteristics were associated with AAWS with enzalutamide. The occurrence of AAWS after enzalutamide was not clinically meaningful. Thus, accounting for this phenomenon in clinical practice or trial designs could be unnecessary.
抗雄激素撤药综合征（AAWS），表现为在停用第一代抗雄激素药物后前列腺特异性抗原（PSA）下降，已得到充分描述。本研究的目的是评估恩杂鲁胺在转移性去势抵抗性前列腺癌男性患者中引发AAWS的发生率。
纳入来自单一机构队列的转移性去势抵抗性前列腺癌患者，这些患者在PSA或影像学进展后停用了恩杂鲁胺。恩杂鲁胺治疗后的AAWS定义为停用恩杂鲁胺后出现的任何PSA下降。比较了恩杂鲁胺治疗后出现和未出现AAWS的患者的基线患者、疾病和治疗特征。基线特征的统计分析包括使用Wilcoxon秩和检验和Fisher精确检验的描述性统计。使用对数秩检验比较恩杂鲁胺治疗的中位持续时间，并使用Kaplan-Meier方法评估出现AAWS患者的无进展生存期。
在47例符合条件的患者中，5例在停用恩杂鲁胺后出现了AAWS。这5例患者的PSA反应分别为84%、32%、17%、15%和15%。直至后续PSA进展的AAWS中位反应时间为3.3个月。恩杂鲁胺停药后出现和未出现AAWS的患者之间，患者、疾病或治疗特征均无差异。
据我们所知，这是迄今为止报道的记录恩杂鲁胺治疗后AAWS发生率和特征的最大队列。恩杂鲁胺治疗后AAWS的发生率较低且持续时间较短。没有患者或疾病相关特征与恩杂鲁胺引发的AAWS相关。恩杂鲁胺治疗后AAWS的发生在临床上并无意义。因此，在临床实践或试验设计中考虑这一现象可能没有必要。
