标签：  恩杂鲁胺

ABSTRACT:Abstract(#br)Background(#br)Enzalutamide is an androgen receptor inhibitor with a demonstrated overall survival benefit in metastatic castration-resistant prostate cancer. A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer (HNPC) showed a high response rate for the prespecified primary endpoint (ie, prostate-specific antigen [PSA] response at week 25), regardless of metastases at baseline, and favorable tolerability.(#br)Objective(#br)To determine the long-term efficacy and safety of enzalutamide monotherapy at 1 and 2 yr.(#br)Design, setting, and participants(#br)Open-label, single-arm study in patients with HNPC and noncastrate testosterone (≥230 ng/dl).(#br)Intervention(#br)Oral enzalutamide 160<ce:hsp sp="0.25"/>mg/d until disease progression or unacceptable toxicity.(#br)Outcome measurements and analysis(#br)PSA response (≥80% decline from baseline) assessed at 1 yr (49 wk) and 2 yr (97 wk).(#br)Results and limitations(#br)The median (range) age was 73 (48–86) yr and 26 patients (39%) presented with metastases at study entry. Of 67 patients enrolled, 45 (67%) remained on enzalutamide at week 97. For patients remaining on therapy, the PSA response rate at week 97 was 100% (95% confidence interval 92–100%). Of 26 patients with metastases at baseline, 13 (50%) had a complete and four (15.4%) had a partial response as best overall tumor response up to 97 wk on treatment. There was overall maintenance of total-body bone mineral density (BMD) and moderate changes in lean and fat body mass at 49 and 97 wk. The most common adverse events were gynecomastia, nipple pain, fatigue, and hot flushes. The study limitations include lack of a control group and of endocrine, glycemic, and lipid data at 97 wk.(#br)Conclusions(#br)Long-term enzalutamide monotherapy in men with noncastrate HNPC is associated with large sustained reductions in PSA, signals indicating a favorable tumor response, and favorable safety/tolerability profile, with relatively small negative effects on total-body BMD.(#br)Patient summary(#br)In this long-term follow-up of the efficacy and safety of enzalutamide monotherapy in patients with hormone-naïve prostate cancer, enzalutamide maintained long-term reductions in prostate-specific antigen, with a minimal impact on total-body bone mineral density.(#br)Trial registration(#br)NCT01302041 。

恩杂鲁胺是由美国Medivation制药公司和日本Astellas制药公司联合研发的新型抗列腺癌治疗药物,于2012年8月31日经美国食品药品监督管理局(FDA)批准上市,专门用于治疗去势抵抗性前列腺癌(CRPC)。由于恩杂鲁胺具有良好的疗效和安全性,市场潜力巨大,其合成研究已经引起了药物化学工作者的重大关注。现已报道的合成方法各有其优势和弊端,因此,开发新的成本更低、收率更高、反应更简洁的合成路线和工艺具有较大的实际意义和价值。

恩杂鲁胺是第2代的雄激素受体拮抗药,其可抑制雄激素信号传导通路的多个靶点,包括抑制雄激素与雄激素受体的结合,同时抑制雄激素受体的核移位以及与DNA的相互作用。Ⅲ期随机对照研究证实恩杂鲁胺可以有效延缓转移性去势抗拒前列腺癌的进展,降低其前列腺特异性抗原水平,进展时间、延长总生存期和首次骨骼相关事件发生时间,恩杂鲁胺为去势抵抗前列腺癌患者提供了新的治疗手段,且不良反应少、耐受性良好。 

绘佳医疗