Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue/R35, Cleveland, OH 44195, USA.
Curr Oncol Rep. 2011 Apr;13(2):92-6. doi: 10.1007/s11912-011-0153-4.
The androgen receptor remains the key player in patients with castration-resistant prostate cancer (CRPC). Available agents capable of blocking early adrenal androgen production have limited activity and can lead to significant toxicities. Abiraterone acetate, a pregnenolone analog, is a small molecule that irreversibly inhibits CYP17, a rate-limiting enzyme in androgen biosynthesis. Several clinical trials have demonstrated the safety and efficacy of this compound in men with metastatic CRPC. Recently, a randomized phase 3 trial evaluating abiraterone acetate in docetaxel-refractory CRPC patients demonstrated a survival improvement over placebo-treated patients (14.8 vs 10.9 months; HR 0.646; P < 0.0001). A similar trial in the pre-chemotherapy setting has completed accrual and is undergoing analysis. Here we review the rationale and clinical development of abiraterone acetate in men with CRPC.
雄激素受体仍然是去势抵抗性前列腺癌（CRPC）患者的关键治疗靶点。现有的能够阻断早期肾上腺雄激素生成的药物活性有限，并且可能导致严重的毒性。醋酸阿比特龙是一种孕烯醇酮类似物，是一种小分子，可不可逆地抑制 CYP17，这是雄激素生物合成的限速酶。几项临床试验已经证实了该化合物在转移性 CRPC 男性患者中的安全性和疗效。最近，一项评估醋酸阿比特龙在多西他赛难治性 CRPC 患者中的随机 3 期临床试验显示，与安慰剂组相比，患者的生存时间得到了改善（14.8 个月 vs 10.9 个月；HR 0.646；P<0.0001）。一项类似的化疗前研究已经完成入组并正在进行分析。在这里，我们回顾了醋酸阿比特龙在 CRPC 男性患者中的作用机制和临床开发。
