Department of Medicine, Division of Oncology, Columbia University Medical Center, 161 Fort Washington Avenue, New York, NY 10032, USA.
Curr Urol Rep. 2011 Jun;12(3):173-9. doi: 10.1007/s11934-011-0187-z.
Seven years passed since docetaxel/prednisone demonstrated and overall survival benefit, leading to its approval by the FDA for metastatic castration resistant prostate cancer. In 2010, two new treatments, sipuleucel-T and cabazitaxel, were approved by the United States Food and Drug Administration for men with castration-resistant prostate cancer, based upon improvement in overall survival. The progress that has been made in understanding the biological basis of disease progression, particularly the role of the continued activation of the androgen receptor, have led to new treatments that will further improve survival in these patients. Abiraterone, a drug that depletes both intracellular and extracellular sources of testosterone, demonstrated a 3.9-month improvement in survival in patients who failed docetaxel-based chemotherapy. Other drugs targeting the androgen-receptor axis, such as TAK-700 and MDV3100, have demonstrated significant activity in phase 1 and 2 studies, and are currently in phase 3. Agents that target angiogenesis, bone, and novel apoptotic proteins currently are under investigation, either as single agents or in combination with chemotherapy. The challenge for the development of clinical trials will be how these compounds will be sequenced in the future.
自多西他赛/泼尼松显示出总生存获益并被美国食品药品监督管理局批准用于转移性去势抵抗性前列腺癌以来，已经过去了 7 年。2010 年，基于总生存改善，两种新的治疗方法——sipuleucel-T 和卡巴他赛——被美国食品药品监督管理局批准用于去势抵抗性前列腺癌患者。在理解疾病进展的生物学基础方面取得的进展，特别是雄激素受体持续激活的作用，导致了新的治疗方法，将进一步提高这些患者的生存率。阿比特龙是一种能够耗尽细胞内和细胞外来源的睾丸酮的药物，在接受多西他赛为基础的化疗失败的患者中，其生存得到了 3.9 个月的改善。其他靶向雄激素受体轴的药物，如 TAK-700 和 MDV3100，在 1 期和 2 期研究中表现出显著的活性，目前正在 3 期研究中。针对血管生成、骨骼和新型凋亡蛋白的药物目前正在进行研究，无论是作为单一药物还是与化疗联合使用。临床试验开发的挑战将是这些化合物在未来将如何进行排序。
