ZYKADIA(ceritinib,中文药名：色瑞替尼胶囊）-为新一代治疗小细胞肺癌口服药
美国初次批准：2014
商品名：Zykadia
通用名：ceritinib
曾用名：LDK378
适应证和用途
ZYKADIA是一种激酶抑制剂适用为对克唑替尼[crizotinib]治疗后已进展或不能耐受的间变性淋巴瘤激酶(ALK)-阳性转移非小细胞肺癌(NSCLC)患者的治疗。这个是一种是在根据肿瘤反应率和反应时间在加速批准下被批准的。尚未确定生存或疾病-相关症状改善。可能依验证性试验临床获益证实和描述情况而确定继续批准这个适应证。
剂量和给药方法
每天1次口服750mg。空腹给予ZYKADIA(即，不要餐后2小时内给予)。
剂型和规格
胶囊：150mg
禁忌证
无
警告和注意事项
⑴ 严重和持续胃肠道毒性：在38%患者由于发生腹泻，恶心，呕吐或腹痛调整剂量。如止抗吐药或止泻药无反应不给药，然后减低ZYKADIA剂量。
⑵ 肝毒性：ZYKADIA可能致肝毒性。至少每月监查肝实验室检验。不给药然后减低剂量，或永久终止ZYKADIA。
⑶ 间质性肺疾病(ILD)/肺炎：在4%患者中发生。在被诊断有治疗相关ILD/肺炎患者中永久终止ZYKADIA。
⑷QT间期延长：ZYKADIA可能致QTc间期延长。监视心电图和电解质 in患者有充血性心脏衰竭，缓慢性心律失常，电解质异常，或患者正在用药物已知延长QTc间期。不给药然后减低剂量，或永久终止ZYKADIA。
⑸ 高血糖：ZYKADIA可能致高血糖。监视葡萄糖和如指示开始或优化抗高血糖药物。不给药然后减低剂量，或永久终止ZYKADIA。
⑹ 心动过缓：ZYKADIA可能致心动过缓。定期监视心率和血压。不给药然后减低剂量，或永久终止ZYKADIA。
⑺ 胚胎胎儿毒性：ZYKADIA可能致胎儿危害。忠告有生殖潜能女性对胎儿潜在风险。
不良反应
最常见不良反应(发生率至少25%)为腹泻，恶心，转氨酶升高，呕吐，腹痛，疲乏，食欲减退，和便秘。
药物相互作用
⑴ CYP3A抑制剂和诱导剂：避免ZYKADIA与强CYP3A抑制剂或诱导剂的同时使用。如不可避免同时使用某种强CYP3A抑制剂，减低ZYKADIA的剂量。
⑵ CYP3A和CYP2C9底物：避免ZYKADIA 与有狭窄治疗指数的CYP3A或CYP2C9底物同时使用。
药企：诺华

FDA approves Zykadia for late-stage lung cancer
Breakthrough therapy drug approved four months ahead of review completion goal date
The U.S. Food and Drug Administration today granted accelerated approval to Zykadia (ceritinib) for patients with a certain type of late-stage (metastatic) non-small cell lung cancer (NSCLC).
Zykadia is an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor that blocks proteins that promote the development of cancerous cells. It is intended for patients with metastatic ALK-positive NSCLC who were previously treated with crizotinib, the only other approved ALK tyrosine kinase inhibitor.
Lung cancer is the leading cause of cancer-related deaths among men and women. According to the National Cancer Institute, an estimated 224,210 Americans will be diagnosed with lung cancer, and 159,260 will die from the disease this year. About 85 percent of lung cancers are NSCLC, making it the most common type of lung cancer. However, only 2-7 percent of patients with NSCLC are ALK-positive.
“Today’s approval illustrates how a greater understanding of the underlying molecular pathways of a disease can lead to the development of specific therapies aimed at these pathways,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug eva luation and Research. “It also demonstrates the FDA’s commitment to working cooperatively with companies to expedite a drug’s development, review and approval, reflecting the promise of the breakthrough therapy designation program.”
Zykadia is the fourth drug with breakthrough therapy designation to receive FDA approval. It is being approved four months ahead of the product’s prescription drug user fee goal date of Aug. 24, 2014, the date the agency was scheduled to complete review of the drug application.
The FDA granted Zykadia breakthrough therapy designation, priority review and orphan product designation because the sponsor demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies; the drug had the potential, at the time of the application was submitted, to be a significant improvement in safety or effectiveness in the treatment of a serious condition; and the drug is intended to treat a rare disease, respectively.
The FDA is approving Zykadia under the agency’s accelerated approval program, which allows approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials.
Zykadia’s safety and effectiveness were established in a clinical trial of 163 participants with metastatic ALK-positive NSCLC. All participants were treated with Zykadia. Results showed that about half of the participants had their tumors shrink, and this effect lasted an average of about seven months.
Common side effects of Zykadia include gastrointestinal symptoms such as diarrhea, nausea, vomiting and abdominal pain. Laboratory abnormalities such as increased liver enzymes, pancreatic enzymes and increased glucose levels were also observed.
Zykadia is marketed by Novartis, based in East Hanover, N.J.
For more information:
FDA: Office of Hematology and Oncology Products
FDA: Approved Drugs: Questions and Answers
FDA: Drug Innovation
FDA: Breakthrough Therapies
NCI: Lung Cancer
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/205755s000lbl.pdf

2014年4月29日美国食品药品监督管理局[FDA]授权加速批准Zykadia(ceritinib)对有某些类型晚期(转移)非小细胞肺癌(NSCLC) 患者。
Zykadia是一种间变性淋巴瘤激酶(ALK)酪氨酸激酶抑制剂阻断促进癌细胞发生蛋白。它意向用于既往唯一被批准ALK酪氨酸激酶抑制剂克唑替尼[crizotinib]治疗过为有转移ALK-阳性NSCLC患者。
肺癌是在男性和妇女中领先癌-相关死亡原因。按照美国国家癌症研究所，估计今年224,210 美国人将被诊断有肺癌，和159,260将死于此病。约85%肺癌为NSCLC，使它为最常见类型肺癌。但是，只有2-7%有NSCLC患者是ALK-阳性。
FDA的药物评价和研究中心血液学和肿瘤学产品室主任Richard Pazdur医学博士说：“今天的批准说明对某种疾病分子通路的更多了解如何能导致发展目标这些通路的特异性治疗”。“它还表明FDA的承诺与企业合作加快药物的开发、审评和批准，反映了突破性治疗程序的承诺。”
Zykadia是接受FDA批准的第四个突破性治疗指定。它正在比2014年8月24日产品的处方药用户收费目标日期提前四个月被批准，监管局计划完成药物申报审评的日期。
FDA授权Zykadia 突破性治疗指定，优先审评和孤儿产品指定因为承办单位药物在申请递交时通过初步临床证据证实可提供大幅改进现有的治疗方法；药物有潜能，分别在治疗某种严重条件将显著改进安全性和有效性；和药物意向治疗某种罕见疾病。
FDA在其加速批准程序下正在批准Zykadia，此程序允许根据临床数据显示药物影响一个替代性终点合理地可能预测对患者的临床获益批准一个治疗严重或危及生命疾病。此程序提供使患者更早得到有前途新药而公司进行验证性临床试验。
在163例有转移ALK-阳性NSCLC参加者一项临床试验确定Zykadia的安全性和有效性。所有参加者被用Zykadia治疗。结果显示约半数参加者有肿瘤皱缩，而这个作用持续平均约7个月。
Zykadia的常见副作用包括胃肠道症状例如腹泻，恶心，呕吐和腹痛。实验室异常例如肝酶，胰腺酶增加和还观察到葡萄糖水平增加。
Zykadia由总部设在新泽西州东汉诺威诺华公司上市。