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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。
Afinitor(everolimus)口服片剂
适应症：肾癌
生产商：Novartis
批准日期：2009年3月30日
瑞士诺华公司的Afinitor口服片剂用于治疗采用其他抗癌药之后病情仍持续恶化的晚期肾癌患者。
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。FDA相关部门表示，Afinitor为那些采用sunitinib或sorafenib治疗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。
适应证和用途
AFINITOR 是一种激酶抑制剂，适用于治疗患者：
（1）胰腺来源的进展性不可切除的，局部晚期或转移性神经内分泌肿瘤(PNET)。尚未确定AFINITOR治疗类癌肿瘤患者中的安全性和有效性.
（2）舒尼替尼[sunitinib]或索拉非尼[sorafenib]治疗失败后的晚期肾细胞癌 (RCC)。
（3）结节性硬化症(TSC)患者的不必立即手术的肾血管平滑肌脂肪瘤。Afinitor治疗肾血管平滑肌脂肪瘤的有效性是基于病人对药物持续反应平均时间为8.3个月，还需进一步的随访。
（3）成人和≥3岁的儿童室管膜下巨细胞性星形细胞瘤(SEGA)伴随结节硬化(TS) ，需要治疗性干预但不是手术切除备选者。AFINITOR的有效性设计根据分析SEGA体积变化. 未曾显示临床效益例如疾病-相关症状改善或总生存增加。
剂量和给药方法
晚期PNET，晚期RCC，或伴TSC的肾血管平滑肌脂肪瘤:
（1）10mg每天1次有或无食物.
（2）对有Child-Pugh类别B肝受损患者，减低AFINITOR剂量至5 mg每天1次。
（3）如需要中度CYP3A4抑制剂和/或P-糖蛋白(PgP)，减低AFINITOR剂量至2.5mg每天1次；如耐受，考虑增加至5 mg每天1次。
（4）如需要CYP3A4的强诱导剂，增加AFINITOR剂量增量至最大20 mg每天1次.
SEGA：
（1）初始剂量根据体表面积与随后调整至得到谷浓度5-10 ng/mL。
（2）如需要中度CYP3A4抑制剂和/或PgP，减低AFINITOR剂量约50%，随后给药应根据治疗性药物监测(TDM)。
（3）如需要CYP3A4的强诱导剂，加倍AFINITOR剂量。随后给药应根据TDM。
为处理不良药物反应可能需要剂量减低和/或中断治疗。
剂型和规格
2.5mg，5mg，和10mg片。
禁忌证
对依维莫司，对其它雷帕霉素[rapamycin]衍生物，或对辅料任何组分超敏。
警告和注意事项
（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。通过减低剂量或停药处理直至症状解决，和考虑使用皮质甾体。
（2）感染：增加感染的风险，有些致命性。监视征象和症状，和及时治疗。
（3）口腔溃疡：口溃疡，口炎，和口粘膜炎是常见的。处理包括口腔洗涤(无酒精或过氧化物)和局部治疗。
（4）肾衰事件：在用AFINITOR治疗患者中曾观察到肾衰病例(包括急性肾衰)，有些有致死性结局。
（5）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
晚期PNET：大多数常见不良反应(发生率≥30%)是口炎, 皮疹, 腹泻, 疲劳，水肿，腹痛，恶心，发热和头痛。
晚期RCC：最常见不良反应(发生率 ≥30%)是口炎，感染，虚弱，疲劳，咳嗽，和腹泻。
伴TSC的肾血管平滑肌脂肪瘤：最常见不良反应（发生率 ≥30%）是口腔炎。
SEGA：最常见不良反应(发生率 ≥30%)是口炎，上呼吸道感染，鼻窦炎，中耳炎，和发热。
药物相互作用
（1）强CYP3A4抑制剂：避免同时使用。
（2）中度CYP3A4和/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的剂量。
特殊人群中的使用
（1）哺乳母亲：终止药物或哺乳，考虑药物对母亲的重要性。
（2）肝受损：在有Child-Pugh类别C肝受损患者中不应使用AFINITOR。对晚期PNET和晚期RCC有Child-Pugh类别B肝受损患者，减低AFINITOR剂量。对SEGA有Child-Pugh类别B肝受损患者，可能不需要调整至起始剂量；然而，随后给药应根据TDM。
Important Safety Information
Patients should not take AFINITOR® (everolimus) if they are allergic to AFINITOR or to any of its ingredients. Patients should tell their health care provider before taking AFINITOR if they are allergic to sirolimus (Rapamune®) or temsirolimus (Torisel®).
AFINITOR can cause serious side effects that can even lead to death. If patients experience these side effects, they may need to stop taking AFINITOR for a while or use a lower dose. Patients should follow their health care provider's instructions. Serious side effects include:
Lung or Breathing Problems: In some patients, lung or breathing problems may be severe and can even lead to death. Patients should tell their health care provider right away if they have any of these symptoms: new or worsening cough, shortness of breath, chest pain, difficulty breathing, or wheezing.
Infections: AFINITOR may make patients more likely to develop an infection, such as pneumonia, or a bacterial, fungal, or viral infection. Viral infections may include reactivation of hepatitis B in people who have had hepatitis B in the past. In some people, these infections may be severe and can even lead to death. Patients may need to be treated as soon as possible. Patients should tell their health care provider right away if they have a temperature of 100.5°F or above, have chills, or do not feel well. Symptoms of hepatitis B or infection may include the following: fever, chills, skin rash, joint pain and inflammation, tiredness, loss of appetite, nausea, pale stools or dark urine, yellowing of the skin, or pain in the upper right side of the stomach.
Kidney Failure: Patients taking AFINITOR may develop kidney failure. In some people, this may be severe and can even lead to death. Patients should have tests to check their kidney function before and during their treatment with AFINITOR.
Delayed Wound Healing: AFINITOR can cause incisions to heal slowly or not heal well. Call your health care provider right away if your incision is red, warm, or painful; if you have blood, fluid, or pus in your incision; if your incision opens up; or if your incision swells.
Before taking AFINITOR, tell your health care provider about all your medical conditions, including if you:
Have or have had kidney problems
Have or have had liver problems
Have diabetes or high blood sugar
Have high blood cholesterol levels
Have any infections
Previously had hepatitis B
Are scheduled to receive any vaccinations. You should not receive a live vaccine or be around people who have recently received a live vaccine during your treatment with AFINITOR. If you are not sure about the type of vaccine, ask your health care provider
Have other medical conditions
Are pregnant or could become pregnant. AFINITOR or AFINITOR DISPERZ can cause harm to your unborn baby. You should use effective birth control while using AFINITOR and for 8 weeks after stopping treatment. Talk to your health care provider about birth control options while taking AFINITOR or AFINITOR DISPERZ
Are breastfeeding or plan to breastfeed. You and your health care provider should decide if you will take AFINITOR or breastfeed. You should not do both
Tell your health care provider about all of the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Using AFINITOR with certain other medicines can cause serious side effects. Keep a list of medicines you take and show it to your health care provider when you get a new medicine. Especially tell your health care provider if you take St John's wort (Hypericum perforatum), medicines that weaken your immune system (your body's ability to fight infections and other problems), or medicines for:
Fungal infections
Bacterial infections
Tuberculosis
Seizures
HIV-AIDS
Heart conditions or high blood pressure
If you are taking any medicines for the conditions listed above, your health care provider might need to prescribe a different medicine or your dose of AFINITOR may need to be changed. Tell your health care provider before you start taking any new medicine.
Common Side Effects: Common side effects include mouth ulcers. AFINITOR can cause mouth ulcers and sores. Tell your health care provider if you have pain, discomfort, or open sores in your mouth. Your health care provider may tell you to use a special mouthwash or gel that does not contain alcohol, hydrogen peroxide, iodine, or thyme.
Other common side effects include:
Infections
Feeling weak or tired
Cough, shortness of breath
Diarrhea and constipation
Skin problems (such as rash, acne, dry skin, or itching)
Nausea and vomiting
Fever
Loss of appetite, weight loss
Swelling of arms, hands, feet, ankles, face, or other parts of the body
Abnormal taste or dry mouth
Inflammation of the lining of the digestive system
Headache
Nose bleeds
Absence of menstrual periods. You may miss one or more menstrual periods. Tell your health care provider if this happens
Pain in arms and legs, mouth and throat, back or joints, or stomach area (abdomen)
Low red blood cells, white blood cells, or platelets
Increased blood cholesterol levels and certain other blood levels
Decreased blood phosphate levels
Increased blood sugar levels
High blood pressure
Difficulty sleeping
Hair loss
Muscle spasms
Feeling dizzy
Nail disorders
Anxiety, aggression, and other abnormal behaviors
Tell your health care provider if you have any side effect that bothers you or does not go away.
These are not all the possible side effects of AFINITOR. For more information, ask your health care provider or pharmacist. Call your doctor for medical advice about side effects.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see full Prescribing Information for AFINITOR, including Patient Information.
The brands listed are the trademarks or register marks of their respective owners and are not trademarks or register marks of Novartis.
Indications
AFINITOR is a prescription medicine used to treat:
Advanced hormone receptor-positive, HER2-negative breast cancer, along with the medicine exemestane, in postmenopausal women who have already received certain other medicines for their cancer
Adults with a type of pancreatic cancer known as pancreatic neuroendocrine tumor (PNET) that has progressed and cannot be treated with surgery. AFINITOR is not for use in people with carcinoid tumors that actively produce hormones
Adults with advanced kidney cancer (renal cell carcinoma or RCC) when certain other medicines have not worked
Adults with a kidney tumor called angiomyolipoma, seen with a genetic condition called tuberous sclerosis complex (TSC), when their kidney tumor does not require surgery right away
The effectiveness of AFINITOR in treating angiomyolipoma of the kidney is based on a study of patients treated over an average of 8.3 months. More information is needed to understand the long-term effects of treatment with AFINITOR
Adults and children with a genetic condition called tuberous sclerosis complex (TSC) who have a brain tumor called subependymal giant cell astrocytoma (SEGA) when the tumor cannot be removed completely by surgery
The effectiveness of AFINITOR is based on change in SEGA size. Improvement in disease-related symptoms or overall survival has not been shown
AFINITOR DISPERZ™ (everolimus tablets for oral suspension) is a prescription medicine used to treat adults and children with a genetic condition called tuberous sclerosis complex (TSC) who have a brain tumor called subependymal giant cell astrocytoma (SEGA) when the tumor cannot be removed completely by surgery.
The effectiveness of AFINITOR is based on change in SEGA size. Improvement in disease-related symptoms or overall survival has not been shown
FDA批准依维莫司的一种新剂型治疗SEGA
8月29日，FDA宣布批准依维莫司的一种新的儿科剂型用来治疗患有罕见脑肿瘤的年幼儿童。这种新配方，依维莫司片作为口服混悬液（Afinitor Disperz），是第一种被批准的儿科专用剂型用来治疗儿童肿瘤，这种新剂型可以快速溶解，提供更小的剂量递增，从而允许更大的给药灵活性。该产品的适应症是治疗室管膜下巨细胞星形细胞瘤（SEGA）。
室管膜下巨细胞星形细胞瘤
依维莫司在2010年获得加速批准的授权治疗伴有结节性硬化症的SEGA患者。该新剂型被推荐用于1岁及以上的伴有结节性硬化症的无法手术SEGA患者，在批准这一新剂型之前，依维莫司不建议在3岁以下儿童中使用。药品标签也进行了更新，包括长期安全性随访数据。
Richard Pazdur教授讲到，合适的儿科剂型可以确保抗癌药物在儿童中使用的安全和有效性。
关于结节性硬化症和SEGA
结节性硬化症是一种罕见的遗传性疾病，由于负调节雷帕霉素靶蛋白（mTOR）的TSC1和TSC2基因缺陷造成的。可导致许多重要器官包括大脑、肾、心脏、眼睛、肺部和皮肤良性肿瘤的增长。SEGA在高达20%的儿童和成人中发生。之前有研究表明mTOR抑制剂对结节性硬化症有深远的影响，包括大脑和皮肤病变的非恶性肿瘤。
迄今为止手术是治疗SEGA的唯一方法，但是侵入性高，因为SEGA往往位于大脑深部，靠近脑室，此外，有些SEGA的病人为双边增长，手术切除很困难。依维莫司及其儿科剂型都获得了加速批准的授权，去治疗伴有结节性硬化症的SEGA病人。
关于依维莫司
依维莫司有诺华公司生产，是抑制mTOR的西罗莫司的衍生物。依维莫司之前已被FDA批准用来治疗多个肿瘤，包括使用其他方法治疗后进展的晚期肾癌（2009年）；胰腺来源的成人进展性晚期神经内分泌肿瘤（2011）；结节性硬化症(TSC)患者的不必立即手术的肾血管平滑肌脂肪瘤（2012）；联合依西美坦治疗激素受体阳性、HER2阴性晚期乳腺癌患者（2012）。
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产地国家: 瑞士
原产地英文商品名:
AFINITOR 2.5mg/tab 30tabs/box
原产地英文药品名:
EVEROLIMUS
中文参考商品译名:
AFINITOR 2.5毫克/片 30片/盒
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 |
