近日，美国食品药品监督管理局（FDA）批准了二氯化镭Ra 223（Xofigo注射剂，拜耳医药保健制药公司）用于治疗去势抵抗性前列腺癌，并伴有骨转移症状和未知原因内脏转移性疾病的病人（详见Xofigo药品说明）。Xofigo是一种发射α粒子的放疗药物，能够模拟钙的作用，并与羟基磷灰石形成复合物以加快骨更新，例如促进骨转移. FDA的药物评价和研究中心血液学和肿瘤产品室主任Richard Pazdur，M.D.说：“Xofigo与骨中矿物质结合直接释放辐射至骨肿瘤，限制对周围正常组织的损伤，”“Xofigo是在去年被FDA批准的显示有延长转移前列腺癌男性生命的第二个前列腺癌药物”。 批准日期：2013年5月23日 公司：拜耳医药 Xofigo(二氯化镭233[radium Ra 223 dichloride])注射剂，为静脉使用 美国初次批准：2013 作用机制 Xofigo的活性部位是α 粒子发射同位素镭-223(为二氯化镭223)，模拟钙和在骨更新增加区与骨矿物质羟基磷灰石形成复合物，例如骨转移(见表2)。α发射体的高线性能量转移(80 keV/微米)导致在临近细胞中双链DNA的高频断裂，导致对骨转移的抗肿瘤作用。来自二氯化镭-223的α粒子范围小于100微米(小于10个细胞直径)限制对周围正常组织损伤。 适应证和用途 Xofigo是一种α粒子发射放射性治疗药物适用为有去势耐受前列腺癌，症状性骨转移和无已知内脏转移病患者的治疗。 剂量和给药方法 Xofigo的给药方案是50kBq (1.35微居里)每kg体重，给予 4周间隔共6次注射。 剂型和规格 单次使用小瓶浓度1,000 kBq/mL(27微居里/mL)在参比日期有总放射性6,000 kBq/小瓶(162微居里/小瓶)在参比日期。 禁忌证 妊娠 警告和注意事项 骨髓抑制：治疗开始前和每剂量Xofigo前测量血计数。如治疗后6至8周内血液学值未恢复终止Xofigo。严密监视患者受损骨髓保留。在尽管支持医护措施仍经受危及生命并发症患者终止Xofigo。 不良反应 接受 Xofigo患者中最常见不良反应(≥10%)是恶心，腹泻，呕吐，和周围水肿。 最常见实验室异常(≥10%)是贫血，淋巴细胞减少，白细胞减少，血小板减少，和中性粒细胞减少。 临床研究 在有症状性骨转移去势耐受前列腺癌患者一项双盲，随机化，安慰剂对照3期临床试验评价Xofigo的疗效和安全性。患者有内脏转移和恶性淋巴结病变超过3 cm被排除。主要疗效终点是总体生存。一个关键第二疗效终点是至首次症状性骨事件(SSE)被定义为由外放疗束(EBRT) 至骨骨症状缓解，新症状性病理性骨折，发生脊髓压迫，或肿瘤相关整形手术干预。对研究未进行计划的放射影像评估。所有患者被基线去除雄激素治疗。在预先计划中期分析截止日期，总共809例患者已被随机化2:1至接受Xofigo 50 kBq(1.35微居里)/kg静脉每4周共6疗程(n = 541)加最佳标准医护或匹配的安慰剂加最佳标准医护(n = 268)。最佳标准医护包括局部EBRT，直至不能接受毒性或细胞毒化疗，其他全身放射性同位素半身EBRT或其他研究性药物的开始。研究排除患者有克罗恩病，溃疡性结肠炎，既往半身辐射或未处理紧迫脊髓压迫。在开始或恢复Xofigo治疗前有骨折，整形手术患者进行稳定化。 平衡组间下列患者人口统计和基线疾病特征。中位年龄为71岁(范围44-94)与种族分布94% 高加索人，4%亚裔，2%黑人和<1%其他。患者被纳入占优势来自欧洲(85%)有4%纳入患者来自北美。86%患者中ECOG体能状态为0-1。85%患者有6或更多骨扫描病变和其中40%有 > 20 病变或superscan。54%患者对癌症相关疼痛使用阿片类疼痛药物，44%患者用非阿片类疼痛药物和2%患者无疼痛药物。患者按基线ALP，双膦酸盐使用，和既往多西紫杉醇暴露分层。41%患者以前使用双膦酸盐和58%既往曾使用多西紫杉醇。在治疗期间，83%的Xofigo 患者和82%安慰剂患者接受促性腺释放激素激动剂[gonadotropin-releasing hormone agonists]和21%的Xofigo患者和34%安慰剂患者同时接受抗雄激素。平衡组间使用全身甾体[steroids](41%)和双膦酸盐(40%)。 包装供应/贮存和处置 Xofigo(二氯化镭223注射剂)以在单次使用小瓶含6 mL溶液浓度1,000 kBq/mL(27微居里/mL)有总放射性6,000 kBq/小瓶(162微居里/小瓶)供应在参比日期(NDC 50419-208-01). 储藏在室温，低于40°C(104°F)。储藏Xofigo在原容器内或等同辐射屏蔽。 这个制备物被核管理委员会或相关协议州相关管理当局批准许可证人制备。 遵守为适当处置和遗弃放射性药物方法[见剂型和给药方法]。 说明书修改资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a398400e-bd31-41a9-9696-4f7c06569ede Xofigo(radium 223 dichloride) Xofigo® Class: Radiopharmaceutical Generic Name: Radium Ra 223 dichloride (RAY-dee-um Ra 223 dye-KLOR-ide) Trade Name: Xofigo® For which conditions is this drug approved? Radium Ra 223 dichloride is indicated for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. What is the mechanism of action? The active component of radium Ra 223 dichloride is the alpha particle-emitting isotope radium-223 (as radium Ra 223 dichloride), which mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover, such as bone metastases The high linear energy transfer of alpha emitters (80 keV/micrometer) leads to a high frequency of double-strand DNA breaks in adjacent cells, resulting in an anti-tumor effect on bone metastases. The alpha particle range from radium-223 dichloride is less than 100 micrometers (less than 10 cell diameters), which limits damage to the surrounding normal tissue. How is radium Ra 223 dichloride typically given (administered)? Radium Ra 223 dichloride is administered by slow intravenous injection over 1 minute. Dosage is determined by body weight (50kBq [1.35 microcurie] per kg body weight) and given at four-week intervals for six injections. Safety and efficacy beyond six injections have not been studied. How are patients typically monitored? Patients will usually have scheduled meetings with their healthcare provider while they are being treated with radium Ra 223 dichloride. Typically, blood will be drawn to check levels of blood cells and to monitor functions of some organ systems, such as the kidneys or liver.  Patients may also undergo physical examinations, scans or other measures to assess side effects and response to therapy. In addition, patients will have blood counts measured prior to treatment initiation and before every dose of radium Ra 223 dichloride. Physicians are advised to discontinue treatment if hematologic values do not recover within six to eights weeks after treatment. Patients with compromised bone marrow reserve should be monitored closely, and radium Ra 223 dichloride should be discontinued in patients who experience life-threatening complications despite supportive care measures. What are the common (occur in 30% or more of patients) side effects of treatment with radium Ra 223 dichloride? Nausea Anemia Lymphocytopenia (insufficient white blood cell counts) Leukopenia (low white blood cell counts) Thrombocytopenia (abnormally low amount of platelets) What are the less common (occur in 10% to 29% of patients) side effects of treatment with radium Ra 223 dichloride? Diarrhea Vomiting Peripheral edema (swelling of ankles, feet, and legs) Neutropenia (low neutrophil count, a type of white blood cell that helps fight infection) This is not a complete list of side effects. Some patients may experience other side effects that are not listed here. Patients may wish to discuss with their physician the other less common side effects of this drug, some of which may be serious. Some side effects may require medical attention. Other side effects do not require medical attention and may go away during treatment. Patients should check with their physician about any side effects that continue or are bothersome. What can patients do to help alleviate or prevent discomfort and side effects? Pay careful attention to the physician’s instructions and inform the physician of any side effects. Maintain adequate rest and nutrition. Eat small meals frequently to help alleviate nausea. If patients have been prescribed an anti-nausea medication, they should be sure to take the prescribed doses. Have blood cell count monitored while receiving radium Ra 223 dichloride. Drink plenty of fluids. (Patients should ask their physician about the amount of liquid to consume during a day.) If possible, avoid large crowds or people who are sick or not feeling well, as this drug may leave some patients susceptible to infection. Wash hands often to reduce the risk of infection. Avoid activities that may cause injury or bruising. Use a soft toothbrush and an electric razor to prevent cuts on the mouth or skin. Are there any special precautions patients should be aware of before starting treatment? There are no restrictions regarding contact with other people after receiving radium Ra 223 dichloride, but patients should follow good hygiene practices while receiving this drug and for at least one week after the last injection in order to minimize radiation exposure from bodily fluids to household members and caregivers. Whenever possible, patients should use a toilet and the toilet should be flushed several times after each use. Clothing soiled with patient fecal matter or urine should be washed promptly and separately from other clothing. Caregivers should use universal precautions for patient care such as gloves and barrier gowns when handling bodily fluids to avoid contamination. Patients who are sexually active should use condoms and their female partners of reproductive potential should use a highly effective method of birth control during treatment and for six months following completion of treatment. When should patients notify their physician? If there are signs of bleeding or infection If there are signs of dehydration, hypovolemia (decreased blood volume), urinary retention, or renal failure/insufficiency What is a package insert?? A package insert is required by the FDA and contains a summary of the essential scientific information needed for the safe and effective use of the drug for healthcare providers and consumers.  A package insert typically includes information regarding specific indications, administration schedules, dosing, side effects, contraindications, results from some clinical trials, chemical structure, pharmacokinetics and metabolism of the specific drug. By carefully reviewing the package insert, you will get the most complete and current information about how to safely use this drug. If you do not have the package insert for the drug you are using, your pharmacist or physician may be able to provide you with a copy.