凡德他尼(vandetanib)是一种合成的苯胺喹唑啉化合物，被称“二代易瑞沙”，为口服的小分子多靶点酪酸激酶抑制剂(TKI)，可同时作用于肿瘤细胞EGFR、VEGFR和RET酪氨酸激酶，还可选择性的抑制其他的酪氨酸激酶，以及丝氨酸/苏氨酸激酶。Ⅰ期临床研究显示剂量限制性毒性为腹泻、高血压和皮疹。常见的毒副作用是腹泻、皮疹、恶心、呕吐以及无症状的QT间期延长。其毒副作用与剂量相关，在<300mg/d时，病人耐受性良好，最大耐受剂量(MTD)为300mg。Ⅱ期临床研究涉及的病种很多。
目前我国正在进行凡德他尼治疗NSCLC的临床试验。
1. 治疗晚期NSCLC（非小细胞肺癌）003号研究比较了凡德他尼 300 mg/d和吉非替尼250mg/d对一线或二线化疗失败的168例晚期NSCLC病人的疗效，与吉非替尼相比，凡德他尼明显地增加了有效率和延长了疾病无进展生存时间，分别为8%和1%，11.9周和8.1周，(P=0.011)。在临床试验中如果病人病情进展或不能耐受毒性，允许其改变治疗方案。试验结果表明，用吉非替尼代替凡德他尼的病人疾病控制率为14%，而用凡德他尼代替吉非替尼的病人疾病控制率达到32%，预计中位总生存期由凡德他尼→吉非替尼为6.1个月，而由吉非替尼→凡德他尼为7.4个月。0007号研究正在进行中，目的是评价凡德他尼联合紫杉醇(200mg/m2)+卡铂(AUC=6)一线治疗ⅢB-IV期NSCLC的疗效。初步试验结果显示，凡德他尼可同时联合传统的化疗药物治疗NSCLC，没有明显增加3~4度的不良反应。
2. 治疗晚期乳腺癌46例，既往接受紫杉醇+蒽环类化疗失败的转移性乳癌患者，接受凡德他尼(100 mg或300mg)，44例可评价的患者中未见客观疗效，2组病人各有1例病情稳定(SD)≥24周，作者认为单药凡德他尼治疗复发耐药的乳腺癌疗效有限，但耐受性良好。
3. 治疗晚期多发性骨髓瘤，18例化疗或造血干细胞移植治疗失败的多发性骨髓瘤患者，口服凡德他尼(100mg)3~29.4周，球蛋白或尿M蛋白未见改善，毒副作用可耐受，常见的毒副作用包括恶心、呕吐、腹泻、皮疹、皮肤瘙痒、感觉障碍等，但未见明确的QT间期改变。
4. 治疗甲状腺癌甲状腺髓样癌发病率低，具有遗传性，无论放射治疗、联合化疗抑或内分泌治疗效果不佳，预后差。0008号研究是一项进行中的、开放的Ⅱ期研究，评估凡德他尼治疗进展期遗传性甲状腺髓样癌的疗效和毒副作用。11例可评价的病人中(接受凡德他尼300mg/d，至少3个月)，2例患者获得PR，9例患者获SD。另外，病人血浆肿瘤标志物降钙素和癌胚抗原分别较基线值下降了72%和25%。目前人们认为，凡德他尼治疗甲状腺髓样癌主要作用于肿瘤细胞靶点RET酪氨酸激酶，RET可促进肿瘤细胞生长和存活，40%的散发性和100%遗传性甲状腺髓样癌有RET基因的过表达。
适应证和用途
Vandetanib是一种激酶抑制剂适用于治疗不能切除，局部晚期或转移的有症状或进展的髓样甲状腺癌。
因为vandetanib治疗相关风险，在惰性，无症状或缓慢进展疾病患者中使用vandetanib应谨慎小心考虑。
剂量和给药方法
（1）300 mg每天1次
（2）在严重毒性事件或QTc间期延长时可能需要减低剂量
（3）有中度和严重肾受损患者中开始剂量应减低至200 mg。
剂型和规格
100mg和300mg片
禁忌证
有长QT综合征患者不要使用vandetanib。
警告和注意事项
（1）曾报道延长的QT间期，尖端扭转型室性心动过速和骤死。在基线，开始vandetanib治疗后2-4周和8-12周，和其后每3个月及剂量调整后，监查心电图和血清钾，钙和TSH水平。当剂量减低适当
（2）曾观察到Stevene-Johnson综合征导致死亡。严重皮肤反应可能促使永远终止vandetanib
（3）曾报道间质性肺疾病征导致死亡。中断vandetanib和研究不能解释呼吸困难，咳嗽，和发热。为间质性肺病应采取适当测量
（4）曾观察到缺血性脑血管事件，出血，心衰，腹泻，甲状腺低下症，高血压，和可逆性后脑白质脑病综合征
（5）当vandetanib给予妊娠妇女可能致死。建议妇女当接受vandetanib和治疗后4个月时避免妊娠
（6）因为QT延长，尖端扭转型室性心动过速和骤死的风险，只能通过严格分配计划被称为vandetanib REMS计划得到vandetanib。只有经认证的处方者和药房能够处方和分配vandetanib。
不良事件
用vandetanib最常见药物不良反应(>20%)曾是腹泻，皮疹，痤疮，恶心，高血压，头痛，疲乏，食欲减退和腹痛。最常见实验室异常(>20%)是钙减低，ALT升高，和葡萄糖减低
药物相互作用
与已知强CYP 3A4诱导剂同时使用可能减低vandetanib药物水平而应避免。
Vandetanib与强CYP 3A4抑制剂伊曲康唑[itraconazole]未显示临床意义药物相互作用。
避免vandetanib与可能延长QT间期药物给药。
Vandetanib Oral tablet
What is this medicine?
VANDETANIB is a medicine for certain types of thyroid cancer.
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.
What should I tell my health care provider before I take this medicine?
They need to know if you have any of these conditions:
bleeding disordersdiarrheaheart diseasehigh blood pressurehigh levels of thyroid-stimulating hormone (TSH) in the bloodhistory of irregular heartbeathistory of low levels of calcium, magnesium, or potassium in the bloodkidney diseaseliver diseaselung or breathing disease, like asthmaseizuresskin conditions or sensitivityan unusual or allergic reaction to vandetanib, other medicines, foods, dyes, or preservativespregnant or trying to get pregnantbreast-feeding
How should I use this medicine？
Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Do not cut, crush, or chew this medicine. Take your medicine at regular intervals. Do not take it more often than directed. Do not stop taking except on your doctor's advice.
A special MedGuide will be given to you by the pharmacist with each prescription and refill. Be sure to read this information carefully each time.
Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.
Overdosage: If you think you've taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.
What may interact with this medicine?
Do not take this medicine with any of the following medications:
arsenic trioxidecertain antibiotics like ciprofloxacin, levofloxacin, moxifloxacincertain antipsychotics like haloperidol, pimozide, sertindole, thioridazine, ziprasidonecertain medicines for irregular heart beat like amiodarone, disopyramide, dofetilide, ibutilide, procainamide, propafenone, quinidine, sotalolcertain medicines for nausea like chlorpromazine, droperidolcertain medicines for seizures like carbamazepine, phenobarbital, phenytoincertain medicines used to treat infections like chloroquine, clarithromycin, erythromycin, pentamidine dexamethasonedolasetrongranisetronmethadonerifampinrifabutinrifapentineSt. John's wort, Hypericum perforatum
This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.
What should I watch for while using this medicine?
Tell your doctor or health care professional right away if you have any change in your eyesight.
You may need blood work done while you are taking this medicine. If you get diarrhea, call your doctor. You may need to have your blood work checked.
Your doctor will monitor your heart while your are taking this medicine. Be sure to keep your appointments.
This medicine can make you more sensitive to the sun. Keep out of the sun while taking this medicine and for 4 months after stopping it. If you cannot avoid being in the sun, wear protective clothing and use sunscreen. Do not use sun lamps or tanning beds/booths.
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you.
Do not become pregnant while taking this medicine. Women should use effective birth control while taking this medicine and for 4 months after stopping it. There is a potential for serious side effects to an unborn child. Talk to your health care professional or pharmacist for more information. Do not breast-feed an infant while taking this medicine.
What side effects may I notice from receiving this medicine?
Side effects that you should report to your doctor or health care professional as soon as possible:
allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tonguebloody or black, tarry stoolsbreathing problemschanges in visionchest pain or palpitationsconfusion, trouble speaking or understandingcoughdiarrheafast, irregular heartbeatfeeling faint or lightheaded, fallsfever, chills, or sore throathigh blood pressurelight-colored stoolsredness, blistering, peeling or loosening of the skin, including inside the mouthred or dark-brown urinered spots on the skinseizuressevere headachesshakinessspitting up blood or brown material that looks like coffee groundssudden numbness or weakness of the face, arm or legsswelling of the legs or anklestrouble walking, dizziness, loss of balance or coordinationunusual bleeding or bruisingunusually weak or tiredyellowing of the eyes or skin
Side effects that usually do not require medical attention (Report these to your doctor or health care professional if they continue or are bothersome.):
loss of appetitenauseastomach paintirednesstrouble sleepingThis list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Where should I keep my medicine?
Keep out of the reach of children.
Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.
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