【商品名】Certican 【通用名】依维莫司 【英文名】Certican 【成份】依维莫司 【适应症】适用于用舒尼替尼[sunitinib]或索拉非尼[sorafenib]治疗失败后晚期肾细胞癌患者的治疗。 【剂量和给药方法】 1、10mg每天1次有或无食物。 2、治疗中断和/或剂量减低至5mg每天1次可能需要处理不良药物反应。 3、对有Child-Pugh类别B肝损伤患者，减低剂量至5mg每天1次。 4、如需要中度CYP3A4或P-糖蛋白(PgP)抑制剂，减低AFINITOR剂量至2.5mg每天1次；如耐受考虑增加至5mg每天1次。 5、如需要CYP3A4的强诱导剂，增加AFINITOR剂量5mg增量至最大20mg每天1次。 【禁忌】对活性物质，对其它雷帕霉素衍生物，或对任何辅料超敏性。超敏性反应比阿姆纤维症状包括，单不限于，过敏，呼吸困难，脸红，胸痛，或胸血管水肿(如，气道或舌肿胀，有或无呼吸损伤)用依维莫司和其它雷帕霉素衍生物曾观察到。 【注意事项】 1、非-感染性肺炎：监查临床症状或放射学变化;曾发生致命性病例.用剂量减低或停药处理直至症状解决,和考虑皮质甾体。 2、感染：增加的风险感染,某些致命性。监视征象和症状,和及时治疗。 3、口腔溃疡：口溃疡,口炎,和口粘膜炎是常见处理包括口腔洗涤(无酒精或过氧化物)和局部治疗。 4、实验室检验改变：可能发生血清肌酐，血糖，和脂质的升高。还可能发生血红蛋白，嗜中性，和血小板减低。治疗前和以后定期监测肾功能，血糖，脂质，和血液学参数。 5、免疫接种：避免活疫苗和密切接触曾接受活疫苗者。 6、妊娠中使用：当给予妊娠妇女时可能发生胎儿危害。告知妇女对胎儿潜在危害。 【不良反应】最常见不良反应(发生率 ≥30%)是口炎，感染，虚弱，疲乏，咳嗽，和腹泻。 【药物相互作用】 1、强CYP3A4或PgP抑制剂：避免同时使用。 2、中度CYP3A4或PgP抑制剂：如需要联用，谨慎使用和减低AFINITOR剂量。 3、强CYP3A4诱导剂：避免同时使用。如不能避免联用，增加AFINITOR剂量。 【在特殊人群中的使用】 1、哺乳母亲：停止药物或哺乳，考虑药物对母亲的重要性。 2、肝损伤：有Child-Pugh类别C肝损伤患者中不应使用AFINITOR。对有Child-Pugh类别B肝损伤患者减低剂量至5mg每天。 【FDA妊娠分级】妊娠类别D 【药理作用】依维莫司是一种mTOR的抑制剂(雷帕霉素哺乳动物靶点)，PI3K/AKT通路下游的一种丝氨酸苏氨酸激酶。在几种人癌中mTOR失调控。依维莫司结合至细胞内蛋白，FKBP-12，导致一种抑制剂性复合物形成和mTOR激酶活性的抑制。依维莫司减低S6核糖体蛋白激酶(S6K1)的活性和真核生物延伸因子4E-结合蛋白(4E-BP)， mTOR的下游效应器，涉及蛋白质合成。此外，依维莫司抑制缺氧-可诱导因子的表达(如，HIF-1)和减低血管内皮生长因子(VEGF)的表达。在体外和/或体内研究中通过依维莫司mTOR的抑制作用曾显示减低细胞增殖，血管生成和葡萄糖摄取。 【储藏】密封保存 【原产地英文商品名】AFINITOR 2.5mg/tab 28tabs/box 【原产地英文药品名】EVEROLIMUS 【中文参考商品译名】 注：以下产品不同规格和不同价格，购买时请以电话咨询为准！ ·AFINITOR 2.5毫克/片 28片/盒 ·Afinitor 28Tablets x5mg/box ·Afinitor 28Tablets x10mg/box 【中文参考药品译名】依维莫司 【生产厂家中文参考译名】Novartis Pharma 【生产厂家英文名】诺华制药 Afinitor(R) Approved In US As First Treatment For Patients With Advanced Kidney Cancer After Failure Of Either Sunitinib Or Sorafenib Novartis announced that Afinitor® (everolimus) tablets has been approved by the US Food and Drug Administration (FDA) for patients with advanced renal cell carcinoma (RCC) after failure of treatment with Sutent® (sunitinib)* or Nexavar® (sorafenib)**. Prior to Afinitor, no other therapy has been studied in a Phase III trial in this patient population where there is an important unmet medical need1. Sutent and Nexavar are commonly used as initial treatments for advanced RCC2. The approval is based on data that showed Afinitor, when compared with placebo, more than doubled the time without tumor growth or death in patients with advanced kidney cancer (4.9 vs. 1.9 months) and reduced the risk of disease progression or death by 67% (hazard ratio=0.33 with 95% confidence interval 0.25 to 0.43; P<0.0001)3. Furthermore, additional data show that after 10 months of treatment with Afinitor, approximately 25% of patients still had no tumor growth1, ***. "This approval provides a new and useful tool for treating advanced renal cell cancer, representing an important step forward in managing this disease," said Robert J. Motzer, MD, attending physician, Memorial Sloan-Kettering Cancer Center, New York and principal investigator of the RECORD-1 trial, the basis for FDA approval of Afinitor. "New treatment options are vital to help us continue to offer patients with advanced kidney cancer new ways to battle their difficult-to-treat disease. Based on clinical trial data, this option should be considered when sunitinib or sorafenib fail." In 2008, the FDA granted priority review status to Afinitor, previously known as RAD001, based on its potential to fill an unmet medical need for patients with advanced kidney cancer. Novartis has filed regulatory submissions in the European Union, Switzerland and Japan, as well as with other regulatory agencies globally1. Afinitor inhibits mTOR, a protein in the cancer cell that controls tumor cell division and blood vessel growth. Preclinical and clinical data have established the important role of mTOR in the development and progression of several types of tumors1. "With this approval, we can now offer patients a targeted therapy proven to fulfill an important unmet need in the treatment of advanced kidney cancer," said David Epstein, President and CEO, Novartis Oncology, Novartis Molecular Diagnostics. "We continue to study Afinitor in kidney cancer, and through a broad clinical program to explore its potential in many other tumor types." About renal cell carcinoma Renal cell carcinoma is often referred to as kidney cancer. Kidney cancer accounts for approximately 2% of all new cancers4. RCC is the most common type of kidney cancer, with occurrence rates rising steadily around the world due in part to smoking and obesity5,6. It is estimated that about 54,000 new cases of RCC developed in the US in 2008 and more than 13,000 people died from the disease7. In RCC, cancer cells develop in the lining of the kidney's tubes and grow into a tumor8. If left untreated, the tumor can spread to neighboring lymph nodes and eventually other organs9. RECORD-1 trial The FDA regulatory filing for Afinitor was based on data from RECORD-1 (REnal Cell cancer treatment with Oral RAD001 given Daily), the largest Phase III clinical trial to study the effects of an oral mTOR inhibitor in advanced RCC patients whose cancer progressed despite prior treatment with sunitinib, sorafenib or both sequentially. In February 2008, based on a recommendation from an independent data monitoring committee, Novartis stopped the trial after interim results showed that patients receiving Afinitor experienced a significant delay in cancer progressing or death compared with patients receiving placebo1. This international, multi-center, randomized, double-blind trial involved 416 patients with advanced RCC whose cancer progressed despite prior treatment with sunitinib, sorafenib or both sequentially. In addition, prior therapy with bevacizumab, interferon alfa and interleukin-2 was allowed. Patients were randomized to receive Afinitor (10 mg) daily or placebo, in conjunction with best supportive care. The primary endpoint of the study was progression-free survival, which was assessed via a blinded independent, central radiological review10. About Afinitor Afinitor is the first oral, daily therapy (5 mg and 10 mg tablets) to treat advanced kidney cancer after failure of treatment with sunitinib or sorafenib. In cancer cells, Afinitor continuously targets mTOR, a protein that acts as a central regulator of tumor cell division, blood vessel growth and cell metabolism. Afinitor is also being studied in multiple cancer types, including neuroendocrine, breast, gastric and hepatocellular carcinoma (HCC), as well as tuberous sclerosis complex (TSC) and non-Hodgkin's lymphoma11. The active ingredient in Afinitor is everolimus, which is available in different dosage strengths under the trade name Certican® for the prevention of organ rejection in heart and kidney transplant recipients. Certican was first approved in the EU in 2003. Certican is not approved for use in the US1. Important safety information Afinitor is contraindicated in patients with hypersensitivity to everolimus, to other rapamycin derivatives or to any of the excipients. Potentially serious adverse reactions include non infectious pneumonitis and infections for which patients should be monitored carefully and treated as needed. In addition, non-infectious pneumonitis may require temporary dose reduction and/or interruption or discontinuation. Patients with systemic invasive fungal infections should not receive Afinitor. Oral ulceration is a common side effect with Afinitor. Renal function, blood glucose, lipids and hematological parameters should be evaluated prior to the start of therapy with Afinitor and periodically thereafter. Strong or moderate CYP3A4 or P-glycoprotein inhibitors should be avoided. An increase in the dose of Afinitor is recommended when co-administered with a strong CYP3A4 inducer. Live vaccinations and close contact with those who have received live vaccines should be avoided. Afinitor should not be used in patients with severe hepatic impairment. Afinitor may cause fetal harm in pregnant women. The most common adverse reactions (incidence ≥30%) were stomatitis, infections, asthenia, fatigue, cough and diarrhea. The most common grade 3/4 adverse reactions (incidence ≥3%) were infections, dyspnea, fatigue, stomatitis, dehydration, pneumonitis, abdominal pain and asthenia. The most common laboratory abnormalities (incidence ≥50%) were anemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, lymphopenia and increased creatinine. The most common grade 3/4 laboratory abnormalities (incidence ≥3%) were lymphopenia, hyperglycemia, anemia, hypophosphatemia and hypercholesterolemia. Deaths due to acute respiratory failure (0.7%), infection (0.7%) and acute renal failure (0.4%) were observed for patients receiving Afinitor. Disclaimer The foregoing release contains forward-looking statements that can be identified by terminology such as "risk," "options," "potential," "continue to study," "explore," "estimated," "can" or similar expressions, or by express or implied discussions regarding potential new indications or labeling for Afinitor, potential approvals of Afinitor in additional markets, or regarding potential future revenues from Afinitor. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with Afinitor to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Afinitor will be approved for sale in any additional markets. Neither can there be any guarantee that Afinitor will be approved for any additional indications or labeling in any market. Nor can there be any guarantee that Afinitor will achieve any particular levels of revenue in the future. In particular, management's expectations regarding Afinitor could be affected by, among other things, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; the impact that the foregoing factors could have on the values attributed to the Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise. About Novartis Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG which provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, preventive vaccines, diagnostic tools, cost-saving generic pharmaceuticals and consumer health products. Novartis is the only company with leading positions in these areas. In 2008, the Group's continuing operations achieved net sales of USD 41.5 billion and net income of USD 8.2 billion. Approximately USD 7.2 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 96,700 full-time-equivalent associates and operate in more than 140 countries around the world. FDA批准Afinitor口服片剂用于治疗晚期肾癌 近日，FDA批准Afinitor（everolimus）口服片剂用于治疗那些采用了其他抗癌药之后病情仍持续恶化的晚期肾癌患者。  肾细胞癌是最常见的肾癌类型，病发于肾小管上皮细胞。通常，这类患者体内的癌细胞对放疗和化疗等标准疗法会产生抵抗性，从而使大多数人通过肾脏摘除达到治疗目的。若患者的癌变部位仅限定在肾脏，60-70%的人生存期可达到5年，但癌细胞一旦发生转移，则患者生存期将会大幅降低。 FDA相关部门负责人表示，Afinitor为那些采用了sunitinib或sorafenib后失败的患者提供了一种全新的治疗选择，像Afinitor这样具有靶向作用的药物可以让患者在病情无恶化的情况下延长存活时间。 Afinitor属激酶抑制剂，它可以妨碍细胞之间的信息传达，阻止肿瘤生长。该药也可用于那些曾采用过其他激酶抑制剂（如Sutent或Nexavar）的晚期肾细胞癌患者。Sutent和Nexavar属于多靶点型激酶抑制剂，即可以同时作用于多个细胞。而Afinitor则通过阻断一种特定的蛋白质（人雷帕霉素靶蛋白/mTOR）起作用，干扰癌细胞的生长、分裂和新陈代谢。 依维莫司—晚期肾癌的新选择 依维莫司—晚期肾癌的新选择。3月30日美国FDA批准依维莫司用于肾癌。研究结果显示，依维莫司可明显增加癌症病人的无进展生存期，对于经舒尼替尼或索拉非尼治疗无效的晚期肾细胞癌病人，依维莫司提供了一个新的治疗选择。 2009年3月30日，诺华公司原免疫抑制药物依维莫司（everolimus，Afinitor）用于肾癌获得美国FDA批准。2008年11月，FDA要求补充数据而将本品的注册延迟了3月，而现在它给与了放行的绿灯。 诺华制药部总裁JoeJimenez接受采访时表示，“依维莫司确实是一个有潜力治疗多种肿瘤的药物，甚至在开始进行乳癌、胃癌和非小细胞肺癌研究之前，我们就相信它将成为一个重磅炸弹级产品。对于诺华来说，它是一个重要产品。 依维莫司是西罗莫司（sirolimus，又称雷帕霉素，即rapamycin）的衍生物，故依维莫司又称40-O-（2-羟乙基）-雷帕霉素，或40-O-（2-羟乙基）-西罗莫司。 依维莫司是一个特异性抑制mTOR分子（哺乳动物雷帕霉素靶蛋白）的药物。临床上主要用来预防肾移植和心脏移植手术后的排斥反应。其作用机制主要包括免疫抑制作用、抗肿瘤作用、抗病毒作用、血管保护作用。常与环孢素等其他免疫抑制剂联合使用以降低毒性。 FDA药物评审中心肿瘤药物评审处主任RobertJustice医生评论道，“对于经舒尼替尼或索拉非尼治疗无效的晚期肾细胞癌病人，依维莫司提供了一个新的治疗选择。试验结果表明，像依维莫司这样的靶向治疗药物可明显增加癌症病人的无进展生存期。” 肾细胞癌是最常见的肾癌，对化疗和放疗反应往往欠佳，初始治疗方法常为手术切除肿瘤。未发生转移的肾细胞癌病人的五年存活率为60-70%。已发生癌细胞转移的晚期癌症病人的生存率明显降低。 Afinitor(everolimus，依维莫司片)被批准用于治疗无效的晚期肾癌患者 RAD001在美国获得优先审查用于满足那些使用其他药物治疗不能获得疗效的晚期肾癌患者 • RAD001提议的商品名为Afinitor®，已在美国、欧洲和瑞士申报。 • 目前The Lancet发表的数据显示RAD001可降低疾病进展风险70%并延长至疾病进展时间达一倍以上。 • RAD001作为每天一次的口服用药，通过持续地对mTOR的靶向抑制作用，对于晚期肾癌患者显示出良好的前景。 日前，诺华对外宣布RAD001（everolimus，依维莫司片）已经获得FDA的快速审批。这个决定是基于该药物的潜在性能即对于使用常规治疗失败的晚期肾癌患者作为首选用药，RAD001显示出卓越的疗效。 诺华也向EMEA (European Medicines Agency) 和Swissmedic (the Swiss Agency for Therapeutic Products) 提出了RAD001市场授权申请。对于RAD001，诺华提议的商品名Afinitor®, 已经获得EMEA的批准同时在美国处于审批阶段。 申报是基于试验RECORD-1 （肾细胞癌患者每天口服RAD001作为治疗）获得的数据。试验的中期研究结果已经发表在2008年7月23日的The Lancet上以及今年早些时候的ASCO大会上。试验数据显示对于那些采用常规治疗方法失败的晚期肾癌患者，RAD001在至肿瘤进展时间和降低疾病进展风险这两个指标方面均显示出疗效1。 “目前，对于那些采用常规治疗手段失败的晚期肾癌患者没有什么更好的治疗方法，”诺华肿瘤，发展部全球负责人、副总裁，医学博士Alessandro Riva介绍说, “现在RAD001得到的最新数据表明它能进一步为上述患者带来充满前景的新治疗方法。” FDA的优先审查地位是给予那些有可能填补目前未满足医疗需要的药品。 有关肾细胞癌 (RCC) 发生在肾或肾细胞的癌症，在全球新发生癌症中占2%并且有不断增长的趋势2。 对其他靶向治疗无效的mRCC患者，RAD001可改善其PFS Motzer等报道，与安慰剂比较，RAD001（everolimus）在改善其他靶向药物治疗转移性肾癌（mRCC）进展后患者的无进展生存（PFS）上有显著地统计学意义和临床意义，并表现出良好的安全性。 该研究入组接受索拉非尼、舒尼替尼或两药联用少于6个月、或疾病进展的透明细胞型RCC患者362例，按2:1的比例随机分入RAD001（10 mg/d po）组和安慰剂组，并均给予最佳支持治疗。安慰剂治疗患者疾病进展时给予RAD001治疗。主要终点为PFS。