恩杂鲁胺（MDV3100）在多西他赛和阿比特龙预处理的转移性去势抵抗性前列腺癌（CRPC）患者中的抗肿瘤活性。
Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone.
机构信息
Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Downs Road, Sutton, Surrey, UK.
Guy's and St. Thomas' NHS Foundation Trust, Great Maze Pond, London, UK.
出版信息
Eur J Cancer. 2014 Jan;50(1):78-84. doi: 10.1016/j.ejca.2013.08.020. Epub 2013 Sep 25.
BACKGROUND
The new generation anti-androgen enzalutamide and the potent CYP17 inhibitor abiraterone have both demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. Preliminary data on the antitumour activity of abiraterone after enzalutamide have suggested limited activity. The antitumour activity and safety of enzalutamide after abiraterone in metastatic CRPC patients is still unknown.
PATIENTS AND METHODS
We retrospectively identified patients treated with docetaxel and abiraterone prior to enzalutamide to investigate the activity and safety of enzalutamide in a more advanced setting. Prostate specific antigen (PSA), radiological and clinical assessments were analysed.
RESULTS
39 patients with metastatic CRPC were identified for this analysis (median age 70years, range: 54-85years). Overall 16 patients (41%) had a confirmed PSA decline of at least 30%. Confirmed PSA declines of ⩾50% and ⩾90% were achieved in 5/39 (12.8%) and 1/39 (2.5%) respectively. Of the 15 patients who responded to abiraterone, two (13.3%) also had a confirmed ⩾50% PSA decline on subsequent enzalutamide. Among the 22 abiraterone-refractory patients, two (9%) achieved a confirmed ⩾50% PSA decline on enzalutamide.
CONCLUSION
Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population.
背景
新一代抗雄激素恩扎鲁胺和强效 CYP17 抑制剂阿比特龙在多西他赛治疗后进展的转移性去势抵抗性前列腺癌（CRPC）患者中均显示出生存获益。阿比特龙治疗后恩扎鲁胺的抗肿瘤活性的初步数据表明其活性有限。转移性 CRPC 患者在接受阿比特龙治疗后应用恩扎鲁胺的抗肿瘤活性和安全性尚不清楚。
患者和方法
我们回顾性地确定了在接受恩扎鲁胺治疗前接受多西他赛和阿比特龙治疗的患者，以研究在更晚期的情况下恩扎鲁胺的活性和安全性。分析了前列腺特异性抗原（PSA）、影像学和临床评估。
结果
对这一分析共确定了 39 例转移性 CRPC 患者（中位年龄 70 岁，范围：54-85 岁）。总体上，有 16 名患者（41%）的 PSA 确有至少下降 30%。有 5/39（12.8%）名患者的 PSA 下降 ⩾50%，1/39（2.5%）名患者的 PSA 下降 ⩾90%。在对阿比特龙有反应的 15 名患者中，有 2 名（13.3%）患者在随后接受恩扎鲁胺治疗时也有确证的 ⩾50%PSA 下降。在 22 名阿比特龙耐药的患者中，有 2 名（9%）患者在接受恩扎鲁胺治疗时确证 PSA 下降 ⩾50%。
结论
我们的初步病例系列数据表明，恩扎鲁胺在多西他赛和阿比特龙治疗后的患者人群中的活性有限。
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