曲美替尼(Trametinib)-2013年5月29日，FDA批准的抗癌药，用于治疗黑色素瘤。曲美替尼是MEK1和MEK2(mitogen-activated protein kinase)的酶抑制剂，由GSK研发，商品名Mekinist。
曲美替尼是一种研究中的MEK 1/2抑制剂，一项纳入了98例葡萄膜黑色素瘤患者的2期交叉研究的最终结果显示，与替莫唑胺相比，曲美替尼应用后疾病控制时间是前者的2倍多，而且在所有接受曲美替尼治疗的患者中，有一半的患者瘤体较以前缩小。这项临床试验第一次鉴定了一种能改善晚期眼部黑色素瘤患者临床结局的药物，Richard D. Carvajal说道，他在美国临床肿瘤协会（ASCO）年会上公布了这些数据。
 “曲美替尼是治疗转移性葡萄膜黑色素瘤的新标准，”他在新闻发布会中公布结果时说道。在此研究之前，没有任何证据能证明某种系统治疗是确实对这个疾病有效的。在过去的10年中，有8项临床试验进行了这方面的研究，纳入的共计157例患者中只有2例经所谓的新治疗方法治疗后有效，这些方法包括化疗、靶向治疗以及免疫治疗。
 “我们目前还没有官方的同情性用药计划；但是，我们将重现开展这项试验，同时采取非随机的方式，这样就可以让更多的患者通过这种方式使用曲美替尼治疗，”他在会后的一次采访中谈道。美国每年约有2，000人诊断为葡萄膜黑色素瘤，它的生物学特性与皮肤黑色素瘤的不同使其成为了一种孤立疾病。
在这项研究中，98例患有转移性眼部黑色素瘤的患者随机分为两组，48例接受曲美替尼治疗，50例接受替莫唑胺治疗。根据实体瘤疗效评价标准（RECIST）的影像学表现，，接受替莫唑胺治疗后恶化的患者允许交替到曲美替尼组。不同组患者的反应类型如下，替莫唑胺组46例可评估患者中有11%（RECIST反应，0%）肿瘤回退，而曲美替尼组46例可评估患者中这一比例达到了50% (RECIST反应，15%)，两者的危险度非常明显，达到了0.46，来自纽约凯瑟琳肿瘤中心的Carvajal博士报道。
曲美替尼组患者的无进展生存期延长了13周，替莫唑胺组的则延长了7周。曲美替尼组的总体生存期为10.8个月，替莫唑胺组为9.4个月。两组中均有超过90%的患者合并有转移性肝脏疾病，超过50%的患者乳酸脱氢酶升高，Carvajal博士写道。而且，该研究中替莫唑胺组的患者在接受治疗4周无任何治疗反应时允许交叉到曲美替尼组；替莫唑胺组80%的患者交叉去接受曲美替尼治疗。
MEK蛋白是MAPK信号通路中的一个关键分子，它是由Gnaq和Gna 11基因突变激活的，曲美替尼可以阻断该蛋白，这一现象在该研究中84%的葡萄膜黑色素瘤患者中观察到。曲美替尼同时也在研究用于甲状腺和肺部肿瘤的治疗，当前有曲美替尼和其他药物联合应用治疗上述疾病的试验正在进行中。     
Carvajal博士提到另外一种MEK抑制剂trametinib（Mekinist，葛兰素史克），最近成为第一个经过食品药品管理局（FDA）许可的MEK抑制剂。Trametinib于2013年5月获得批准，它是作为一种用于患有无法切除/转移黑色素瘤同时合并BRAF V600E或V600K突变的成人患者的单一口服用药获批的。

MEKINIST(trametinib Tablets)为口服片使用
批准日期：2013年5月29日；公司: GlaxoSmithKline
作用机制
Trametinib 是一种有丝分裂原-激活的胞外信号调控激酶1(MEK1)和MEK2激活以及MEK1和MEK2激酶活性的可逆性抑制。MEK蛋白胞外信号-相关激酶 (ERK)通路的上游调节物，促进细胞增殖作用。BRAF V600E突变导致BRAF通路的结构性激活其中包括MEK1和MEK2。Trametinib抑制BRAF V600突变-阳性黑色素瘤细胞在体外和体内生长。
适应证和用途
MEKINIST是一种适用于治疗有不可切除的或转移黑色素瘤当用FDA批准测试检验有BRAF V600E或V600K突变患者。
使用限制：MEKINIST不适用于治疗以前曾接受BRAF抑制剂治疗患者。
剂量和给药方法
（1）开始用MEKINIST治疗前确证在肿瘤标本存在BRAF V600E或V600K突变。
（2）推荐剂量是2 mg口服每天1次服用至少1小时前或进餐后至少2小时。
注：(BRAF是一个人基因使一种被称为B-Raf的蛋白。基因还称为原-癌基因B-Raf和v-Raf鼠类肉瘤病毒原癌基因同源B1, 而这个蛋白更以前被称为丝氨酸/苏氨酸蛋白激酶B-Raf)
剂型和规格
片：0.5mg，1mg，和2mg。
禁忌证
无。
警告和注意事项
（1）心肌病：一个月治疗后再评估LVEF，和其后约每2至3个月评价。
（2）视网膜色素上皮脱落(RPED)：对任何视觉障碍进行眼科评价。如被诊断RPED不给MEKINIST和如3个月后无改善终止。
（3）视网膜静脉阻塞(RVO)：终止MEKINIST.
（4）间质性肺疾病(ILD)：不给MEKINIST对新或进展性不能解释的肺症状或发现，例如咳嗽，呼吸困难，缺氧，或浸润。为治疗-相关ILD或肺炎永远终止MEKINIST。
（5）严重皮肤毒性：监视皮肤毒性和继发感染。对不能耐受2级，或3或4级皮疹尽管MEKINIST的中止在3周内未改善终止。
（6）胚胎胎儿毒性：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
对MEKINIST最常见不良反应(≥20%)包括皮疹，腹泻，和淋巴水肿。
为报告怀疑不良反应，联系GlaxoSmithKline电话1-888-825-5249或FDA电话1-800-FDA-1088或www.fda.gov/medwatch.
特殊人群中使用
（1）哺乳母亲：终止药物或哺乳。
（2）女性和男性的生殖潜能：忠告女性患者对妊娠计划和预防。可能损害生育能力。
Mekinist
Generic Name: trametinib
Date of Approval: May 29, 2013
Company: GlaxoSmithKline
Treatment for: Advanced Melanoma
FDA Approves Mekinist
The U.S. Food and Drug Administration (FDA) has approved Mekinist (trametinib), a kinase inhibitor, as a single-agent oral treatment for unresectable or metastatic melanoma in adult patients with BRAF V600E or V600K mutations. Mekinist is not indicated for the treatment of patients who have received a prior BRAF inhibitor therapy. The mutation must be detected by an FDA-approved test, such as the companion diagnostic assay from bioMérieux S.A., THxID™-BRAF.
Mekinist Patient Information
Read the Medication Guide that comes with Mekinist before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is Mekinist?
Mekinist is a prescription medicine used to treat people with a type of skin cancer called melanoma:
•that has spread to other parts of the body or cannot be removed by surgery, and
•that has a certain type of abnormal "BRAF" gene.
Mekinist should not be used to treat people who have received a BRAF inhibitor for treatment of their melanoma.
Your healthcare provider will perform a test to make sure that Mekinist is right for you.
It is not known if Mekinist is safe and effective in children.
What should I tell my healthcare provider before taking Mekinist?
Before you take Mekinist, tell your healthcare provider if you:
•have heart problems
•have lung or breathing problems
•have eye problems
•have high blood pressure (hypertension)
•have liver or kidney problems
•have any other medical conditions
•are pregnant or plan to become pregnant. Mekinist can harm your unborn baby.
•Women who may become pregnant should use effective birth control (contraception) during treatment with Mekinist and for four months after stopping treatment. Talk to your healthcare provider about birth control methods that may be right for you. Tell your healthcare provider right away if you become pregnant during treatment with Mekinist.
•are breastfeeding or plan to breastfeed. It is not known if Mekinist passes into your breast milk. You and your healthcare provider should decide if you will take Mekinist or breastfeed. You should not do both.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.
How should I take Mekinist?
•Take Mekinist exactly as your healthcare provider tells you to take it. Do not change your dose or stop Mekinist unless your health care provider tells you.
•Take Mekinist one time a day.
•Take Mekinist one hour before or two hours after meals.
•If you miss a dose, take it as soon as you remember. If it is within 12 hours of your next scheduled dose, skip the missed dose. Just take the next dose at your regular time.
•If you take too much Mekinist, call your healthcare provider or go to the nearest hospital emergency room right away.
Mekinist side effects
Mekinist may cause serious side effects, including:
•heart problems, including heart failure. Your healthcare provider should check your heart function before you start taking Mekinist and during treatment. Signs and symptoms of heart problems may include:
◦feeling like your heart is pounding or racing
◦shortness of breath
◦swelling of your ankles and feet
◦feeling lightheaded
•eye problems. Mekinist can cause eye problems including blindness. Tell your healthcare provider right away if you get these symptoms of eye problems:
◦blurred vision, loss of vision, or other vision changes
◦see color dots
◦halo (seeing blurred outline around objects)
•lung or breathing problems. Tell your healthcare provider if you have any new or worsening symptoms of lung or breathing problems, including:
◦shortness of breath
◦cough
•skin rash. Rash is the most common side effect of Mekinist and in some cases can be severe and can result in admission to the hospital if severe. Tell your healthcare provider if you get any of the following symptoms:
◦skin rash
◦acne
◦redness, swelling, peeling, or tenderness of hands or feet
◦skin redness
The most common side effects of Mekinist include:
•diarrhea
•swelling of the face, arms, or legs
Mekinist can cause new or worsening high blood pressure (hypertension). Your healthcare provider should check your blood pressure during treatment with Mekinist. Tell your healthcare provider if you develop high blood pressure, your blood pressure worsens, or you have severe headache, lightheadedness, or dizziness.
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of Mekinist. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Mekinist?
•Store Mekinist in the refrigerator between 36°F to 46°F (2°C to 8°C). Do not freeze.
•Keep Mekinist dry and away from moisture.
•The bottle of Mekinist contains a desiccant packet to help keep your medicine dry. Do not throw away the desiccant packet.
•Keep Mekinist in its original bottle. Do not place tablets in a pill box.
•Safely throw away Mekinist that is out of date or no longer needed.
Keep Mekinist and all medicine out of the reach of children.
General information about Mekinist
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information Leaflet. Do not use Mekinist for a condition for which it was not prescribed. Do not give Mekinist to other people, even if they have the same symptoms that you have. It may harm them.
You can ask your healthcare provider or pharmacist for information about Mekinist that is written for health professionals.
For more information, go to www.mekinist.com or call 1-888-825-5249.
What are the ingredients in Mekinist?
Active ingredient: trametinib
Inactive ingredients:
Tablet Core: mannitol, microcrystalline cellulose, hypromellose, croscarmellose sodium, magnesium stearate (vegetable source), sodium lauryl sulfate, colloidal silicon dioxide.
Tablet Coating: hypromellose, titanium dioxide, polyethylene glycol, polysorbate 80 (2-mg tablets), iron oxide yellow (0.5-mg tablets), iron oxide red (2-mg tablets).