近日，美国食品药品管理局近日批准了Xtandi(enzalutamide)用于已出现扩散或复发的去势抵抗性前列腺癌晚期 (转移) 患者，对于该类型患者，即便采用可最大降低睾酮水平的药物疗法或手术疗法仍会出现扩散或复发。 Xtandi此前曾被批准与另一种抗癌药物-多西他赛联用治疗前列腺癌患者，该项目当时被 FDA编入优先评审程序参与评审。根据该程序，在治疗方面可能具有主要优势的药物或对于目前尚没有适当疗法的治疗药物，有望获得为期6个月的快速审批。Xtandi的处方药消费者付费目标日期为 2012年11月22日，而最终该产品获得FDA批准的时间较之提前了3个月。“对于患者来说，重要的是还需要治疗晚期前列腺癌的新方法。” FDA药物评价与研究中心血液与肿瘤学制品办公室主任、医学博士Richard Pazdur说，“作为治疗该病最新的药物，Xtandi 具有延长患者生命的能力。 批准日期：2014年9月10日，公司：安斯泰来（Astellas） XTANDI（恩杂鲁胺[enzalutamide]）胶囊，用于口服 首次美国批准：2012 近期重大变化 适应症及用法：7/2018 剂量和给药， 重要行政指导：7/2018 禁忌症：7/2018 警告和预防措施：7/2018 警告和注意事项，超敏反应：7/2018 警告和注意事项，缺血性心脏病：7/2018 警告和预防措施，Falls和裂缝：7/2018 警告和预防措施，胚胎胎儿毒性：7/2018 作用机理 恩他鲁胺是雄激素受体抑制剂，其作用于雄激素受体信号通路的不同步骤。恩扎鲁胺已被证明竞争性地抑制雄激素与雄激素受体的结合，并因此抑制雄激素受体的核移位及其与DNA的相互作用。一个主要代谢物，N-去甲基泽兰酰胺，表现出类似的体外活性Zealutut酰胺。在异种小鼠前列腺癌移植模型中，恩扎鲁胺在体外抑制了前列腺癌细胞的增殖和诱导细胞死亡，并降低了肿瘤体积。 适应症及用法 XTANDI是一种雄激素受体抑制剂，用于治疗去势抗性前列腺癌患者。 剂量与给药 XTANDI 160mg（四40mg胶囊）每日口服1次。全脂胶囊。XTANDI可以携带或不带食物。 接受XTANDI的患者也应同时接受促性腺激素释放激素（GnRH）类似物或应进行双侧睾丸切除术。 剂型和强度 40mg胶囊 禁忌症 没有。 警告和注意事项 在接受XTANDI的患者中有0.4%发生癫痫发作。在易感因素患者中，2.2%的患者有癫痫发作。在治疗期间发生癫痫发作的患者永久停止XTANDI。 后部可逆性脑病综合征（PRES）：停止XTANDI。 超敏反应：停止XTANDI。 缺血性心脏病：优化心血管危险因素的管理。停止XTANDI为3-4事件。 在接受XTANDI的患者中分别发生了10%和8%的跌倒和骨折。评估患者的骨折和跌倒风险，并根据既定指导方针治疗骨靶向剂。 胎儿胚胎毒性：XTANDI可引起胎儿损伤和妊娠损失。建议男性具有生殖潜能的女性使用有效的避孕方法。 不良反应 XTANDI患者出现的最常见的不良反应（10%以上）为乏力/乏力、食欲减退、潮热、关节痛、头晕/眩晕、高血压、头痛和体重下降。 为了报告可能的不良反应，请联系Astellas Pharma US Inc.在1-800-727-7003或FDA 1-800-FDA-1088或WWW.FDA.GOV/MEDWATCH。 药物相互作用 避免强的CYP2C8抑制剂，因为它们可以增加血浆对XTANDI的暴露。如果联合用药是必要的，减少XTANDI的剂量。 避免强CYP3A4诱导剂，因为它们可以降低血浆暴露于XTANDI。如果联合用药是必要的，增加XTANDI的剂量。 避免CYP3A4、CYP2C9和CYP2C19底物具有狭窄的治疗指数，因为XTANDI可能降低这些药物的血浆暴露。如果XTANDI与华法林（CY2C9底物）联合使用，则进行额外的INR监测。 包装供应/储存和搬运 XTANDI(enzalutamide)40mg胶囊以白色至灰白色长圆形软明胶胶囊的形式提供，用黑色墨水用ENZ压印。XTANDI胶囊有以下包装尺寸： 120瓶胶囊（NDC 04690125-99） 建议储存：XTANDI胶囊在20℃至25℃（68°F至77°F）干燥处储存，并保持容器密闭。允许从15°C到30°C（59°F到86°F）的偏移。 XTANDI不应由患者及其护理人员以外的人处理，尤其是怀孕或可能怀孕的妇女。不要溶解或打开胶囊。 1）：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b129fdc9-1d8e-425c-a5a9-8a2ed36dfbdf 2）：http://www.astellasoncology.com/us/news/fda-approves-supplemental-new-drug-application-for-xtandi-capsules.html Xtandi(enzalutamide)capsules 40mg Manufacturer: Astellas Pharma and Medivation Pharmacological Class: Androgen receptor inhibitor. Active Ingredient(s): Enzalutamide 40mg; caps. Indication(s): Treatment of metastatic castration-resistant prostate cancer in patients who have previously received docetaxel. Pharmacology: Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. Clinical Trials: The efficacy and safety of Xtandi in patients with metastatic castration-resistant prostate cancer who had received prior docetaxel-based therapy were assessed in a randomized, placebo-controlled, multicenter phase 3 clinical trial. The primary endpoint was overall survival. A total of 1199 patients were randomized 2:1 to receive either Xtandi 160mg once daily (N=800) or placebo orally once daily (N=399). All patients continued androgen deprivation therapy. Patients were allowed, but not required to continue or initiate glucocorticoids. Study treatment continued until disease progression (evidence of radiographic progression, a skeletal- related event, or clinical progression), initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal. Patients with a history of seizure, taking medicines known to decrease the seizure threshold, or with other risk factors for seizure were not eligible. The pre-specified interim analysis at the time of 520 events showed a statistically significant improvement in overall survival in patients on the Xtandi arm compared to patients on the placebo arm (number of deaths: 38.5% for Xtandi vs. 53.1% for placebo; median survival: 18.4 months for Xtandi vs. 13.6 months for placebo; P-value: <0.0001; HR: 0.63). Legal Classification: Rx Adults: Swallow whole. 160mg once daily. Dose modifications: ≥Grade 3 toxicity or intolerable side effect: withhold dosing for 1 week or until symptoms improve to ≤Grade 2, then resume at same or reduced dose, if warranted. Concomitant strong CYP2C8 inhibitors: avoid if possible. If co-administration necessary, reduce Xtandi dose to 80mg once daily; if inhibitor is discontinued, return Xtandi dose to dose used prior to initiation of inhibitor. Children: Not established. Contraindication(s): Pregnancy (Cat.X). Warnings/Precautions: Seizure risk. Severe renal or hepatic impairment. Nursing mothers. Interaction(s): Potentiated by strong CYP2C8 inhibitors (eg, gemfibrozil), CYP3A4 inhibitors (itraconazole). May be antagonized by CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin, St. John’s Wort). Antagonizes midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Avoid concomitant drugs with narrow therapeutic indexes metabolized by CYP3A4 (eg, alfentanil, cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus), CYP2C9 (eg, phenytoin, warfarin), CYP2C19 (eg, S-mephenytoin); enzalutamide may decrease their exposure. Caution with concomitant drugs that may lower the seizure threshold. Monitor INR if concomitant warfarin cannot be avoided. Adverse Reaction(s): Asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper respiratory infection, muscular weakness, dizziness, insomnia, lower respiratory infection, spinal cord compression and cauda equina syndrome, hematuria, paresthesia, anxiety, hypertension, neutropenia; seizures. How Supplied: Caps—120