抗癌新药Xtandi(enzalutamide 中文药名 恩杂鲁胺胶囊)获美国及欧洲批准用于治疗已扩散或复发的晚期(转移性)男性晚期前列腺癌，即使其已接受过为减少睾酮的药物或手术治疗。Xtand是一种每日口服1次的雄激素受体抑制剂 批准日期：2012年8月31日；公司：Medivation Inc.和Astellas Pharma Inc. XTANDI（恩杂鲁胺 enzalutamide）胶囊 供口服使用 最初美国批准：2012 目前的主要变化 警告和注意事项 08/2015 剂量调整 08/2015 作用机理 Enzalutamide是雄激素受体抑制剂，作用于雄激素受体信号传导途径的不同步骤。 Enzalutamide已经显示出竞争性抑制雄激素结合于雄激素受体和抑制雄激素受体核易位和相互作用与DNA。一个主要的代谢产物，N去甲基enzalutamide，展出的体外活性类似于enzalutamide。 Enzalutamide体外降低增殖和前列腺癌细胞的诱导的细胞死亡，并在小鼠前列腺癌异种移植模型中减少肿瘤体积。 适应症和用法 XTANDI是用于治疗转移性去势抗性前列腺癌的治疗表明雄激素受体抑制剂。 用法用量 XTANDI 160毫克（4个40毫克胶囊），每天一次口服。吞咽胶囊整体。 XTANDI可采取或没有食物。 剂型和规格 胶囊 40毫克 禁忌症 怀孕 警告和注意事项 •发作发生在接收谁先前接收多西紫杉醇和在患者谁是化疗幼稚0.1％XTANDI患者0.9％。有一个在谁曾癫痫发作患者XTANDI没有临床试用体验。谁在治疗期间制定发作的患者永久性停止XTANDI。 •可逆性后部脑病综合征（PRES）：请停止XTANDI。 不良反应 最常见的不良反应（≥10％）是虚弱/乏力，腰痛，食欲减退，便秘，关节痛，腹泻，潮热，上呼吸道感染，血管神经性水肿，呼吸困难，肌肉骨骼痛，体重明显下降，头痛，高血压，头晕/眩晕。 药物相互作用 •避免强CYP2C8抑制剂，因为它们能提高血浆暴露XTANDI。如果联合给药是必要的，降低XTANDI的剂量。 •避免强CYP3A4诱导剂，因为他们可以降低血浆暴露XTANDI。如果联合给药是必要的，增加XTANDI的剂量。 •避免CYP3A4，CYP2C9和CYP2C19基板具有窄的治疗指数，因为XTANDI可能会降低这些药物的血浆暴露。如果XTANDI是共同给予华法林（CYP2C9底物），进行额外的监测INR。 XTANDI (Enzalutamide) Capsules 40mg Important Safety Information Warnings and Precautions Seizure  In Study 1, conducted in patients with metastatic castration-resistant prostate cancer (CRPC) who previously received docetaxel, seizure occurred in 0.9% of XTANDI patients and 0% of placebo patients. In Study 2, conducted in patients with chemotherapy-naive metastatic CRPC, seizure occurred in 0.1% of XTANDI patients and 0.1% of placebo patients. There is no clinical trial experience readministering XTANDI to patients who experienced a seizure, and limited safety data are available in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold; Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others. Permanently discontinue XTANDI in patients who develop a seizure during treatment. Posterior Reversible Encephalopathy Syndrome (PRES)  In post approval use, there have been reports of PRES in patients receiving XTANDI. PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably MRI. Discontinue XTANDI in patients who develop PRES. Adverse Reactions The most common adverse reactions (≥ 10%) reported from two combined clinical studies that occurred more commonly (≥ 2% over placebo) in XTANDI patients were asthenia/fatigue, back pain, decreased appetite, constipation, arthralgia, diarrhea, hot flush, upper respiratory tract infection, peripheral edema, dyspnea, musculoskeletal pain, weight decreased, headache, hypertension, and dizziness/vertigo. In Study 1, Grade 3 and higher adverse reactions were reported among 47% of XTANDI patients and 53% of placebo patients. Discontinuations due to adverse events were reported for 16% of XTANDI patients and 18% of placebo patients. In Study 2, Grade 3-4 adverse reactions were reported in 44% of XTANDI patients and 37% of placebo patients. Discontinuations due to adverse events were reported for 6% of both study groups. • Lab Abnormalities: Grade 1-4 neutropenia occurred in 15% of XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade 3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade 3-4). • Infections: In Study 1, 1% of XTANDI patients compared to 0.3% of placebo patients died from infections or sepsis. In Study 2, 1 patient in each treatment group (0.1%) had an infection resulting in death.  • Falls (including fall-related injuries), occurred in 9% of XTANDI patients and 4% of placebo patients. Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, joint injuries, and hematomas. •   Hypertension occurred in 11% of XTANDI patients and 4% of placebo patients. No patients experienced hypertensive crisis. Medical history of hypertension was balanced between arms. Hypertension led to study discontinuation in < 1% of all patients. Drug Interactions Effect of Other Drugs on XTANDI  Avoid strong CYP2C8 inhibitors, as they can increase the plasma exposure to XTANDI. If co-administration is necessary, reduce the dose of XTANDI. Avoid strong CYP3A4 inducers as they can decrease the plasma exposure to XTANDI. If co-administration is necessary, increase the dose of XTANDI. Effect of XTANDI on Other Drugs  Avoid CYP3A4, CYP2C9, and CYP2C19 substrates with a narrow therapeutic index, as XTANDI may decrease the plasma exposures of these drugs. If XTANDI is co-administered with warfarin (CYP2C9 substrate), conduct additional INR monitoring. 新药XTANDI(ENZALUTAMIDE)CAPSULE ORAL治疗晚期前列腺癌效果好 美国食品和药物管理局（FDA）8月31日批准Xtandi（enzalutamide）治疗已扩散或复发的晚期（转移性）男性去势抵抗性前列腺癌，即使其已接受过为减少睾酮的药物或手术治疗。 该药物被批准与多西他赛（另一种抗肿瘤治疗药物）联合治疗前列腺癌患者。Xtandi根据FDA的优先审查程序接受了审查。该程序为能够提供重大进展或者在没有足够治疗方案时提供治疗的药物提供一个快速的6个月的审查。 Xtandi获得FDA批准比目标日期2012年11月22日提前了三个月。 “对于晚期前列腺癌，增加治疗方案仍然对患者十分重要”，FDA药品评价和研究中心的血液学和肿瘤学产品办公室主任Richard Pazdur, M.D.说“Xtandi是治疗这种疾病，并且证明其有能力延长病人的生命的最新药物”。 前列腺癌形成于男性生殖系统的腺体，男性荷尔蒙睾丸激素刺激前列腺肿瘤的生长。据美国国家癌症研究所数据，在2012年估计有241740人被诊断患有前列腺癌，28,170将死于这种疾病。 在一项8月15日发表于新英格兰的对照、双盲的3期临床试验结果，证实了Xtandi显着延长化疗后的转移性去势抵抗性前列腺癌男性的生存。 该研究共纳入1199名既往结束过多西他赛治疗的转移性去势抵抗性前列腺癌的患者，根据ECOG评分和疼痛强度分层，将患者以2:1的比例随机分组，有800例患者分到治疗组，接受Xtandi，口服，160毫克/天，安慰剂399例患者。研究的主要终点是要衡量男性接受Xtandi与接受安慰剂（糖丸）相比总生存期（死亡前的时间长度）的变化。 结果显示： 这项研究在达520死亡的中期分析后停止。enzalutamide组的中位总生存期为18.4个月（95％CI 17.3-未达到），而安慰剂组中位生存期为13.6个月（95％CI，11.3-15.8），两组HR 0.63，95％CI 0.53-0.75，P <0.001。治疗组与安慰剂相比的优越性显示在所有次要终点：前列腺特异性抗原（PSA）水平减少50％或更多（54％比2％，P <0.001），软组织反应率（29％比4％，P <0.001），生活质量的缓解率（43％对18％，P<0.001），PSA进展时间（8.3-3.0个月，危险比为0.25， P <0.001），影像学无进展生存期（8.3个月-2.9个月，危险比为0.40，P <0.001），和第一骨相关事件（16.7个月-13.3个月，危险比为0.69，P <0.001）。 在研究中接受Xtandi治疗观察到的最常见的副作用是虚弱或疲劳，腰背痛，腹泻，关节痛，潮热，组织肿胀，肌肉骨骼疼痛，头痛，上呼吸道感染，头晕，压迫脊髓和马尾神经综合征，肌无力，睡眠困难，下呼吸道感染，血尿，刺痛感，焦虑和高血压。 大约1％接受Xtandi的患者癫痫发作，对于发作癫痫的患者停止Xtandi治疗。临床研究排除了在过去发生以下病史的患者：癫痫、意识丧失、12个月内的暂时脑供血不足、中风，脑转移瘤、脑动静脉畸形或服用可能会降低癫痫发作阈值的药物。在这些条件下的患者中Xtandi的安全性是未知的。 Xtandi将由伊利诺州诺斯布鲁克的Astellas Pharma U.S.公司和加州旧金山的Medivation公司合作上市。由此看出，Xtandi在治疗晚期前列腺癌方面的潜力，并发挥了重要作用，希望这些新的治疗能够为患者和医生带来新的出路。 需要提醒患者的是，癌症新药Xtandi为处方药，需要有临床肿瘤科医生诊断和开具处方，同时也需要注意用量及其监测并发症等。 原研药品资料附件： https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b129fdc9-1d8e-425c-a5a9-8a2ed36dfbdf --------------------------------------------------------------- 产地国家：美国 原产地英文商品名: Xtandi 40mg/cap 120caps/box 原产地英文药品名: ESCITALOPRAM 中文参考商品译名: Xtandi 40毫克/胶囊 120胶囊/瓶 中文参考药品译名: 生产厂家中文参考译名: 恩杂鲁胺 安斯泰来 生产厂家英文名: ASTELLAS --------------------------------------------------------------- 产地国家：英国 原产地英文商品名: Xtandi 40mg/cap 112caps/box 原产地英文药品名: ESCITALOPRAM 中文参考商品译名: Xtandi 40毫克/胶囊 112胶囊/盒 中文参考药品译名: 生产厂家中文参考译名: 恩杂鲁胺 安斯泰来 生产厂家英文名: ASTELLAS