Cometriq(cabozantinib)capsules
作用机制
体外生化和/或细胞学分析曾显示cabozantinib抑制RET，MET，VEGFR-1，-2和-3，KIT，TRKB，FLT-3，AXL，和TIE-2的酪氨酸激酶活性。这些酪氨酸激酶受体是涉及正常细胞学功能和病理学过程二者例如肿瘤发生，转移，肿瘤血管生成，和肿瘤微环境的维持。
适应症和用途
COMETRIQ是激酶抑制剂适用为进展性，转移甲状腺髓样癌(MTC)患者的治疗。 剂量和给药方法
● 推荐剂量：140mg口服，每天1次。
● 指导患者服用COMETRIQ前至少2小时和后至少1小时不要进食。
剂型和规格 20 mg和80mg胶囊。
禁忌证:无。
警告和注意事项
● 血栓形成事件：对心肌梗死，脑梗死，或其他严重动脉血栓栓塞事件终止COMETRIQ。
● 伤口并发症：对裂开或需要医学干预并发症不给予COMETRIQ。
● 高血压：有规律地监视血压。对高血压危象终止COMETRIQ。
● 颌骨骨坏死：终止COMETRIQ。
● 掌足红肿综合征(PPES)：中断COMETRIQ，减低剂量。
● 蛋白尿：监视尿蛋白。对肾病综合征终止。
● 可逆性后部白质脑病综合征(RPLS)：终止COMETRIQ。
● 胚胎胎儿毒性：可致胎儿危害。建议妇女对胎儿潜在风险。
不良反应
最常报道药物不良反应(≥25%)是腹泻，口腔炎，掌足红肿综合征(PPES)，体重减轻，食欲不振，恶心，疲乏，口腔痛，发色变化，味觉障碍，高血压，腹痛，和便秘。最常见实验室异常(≥25%)是增加AST，增加ALT，淋巴细胞减少，碱性磷酸酶增加，低钙血症，中性粒细胞减少，血小板减少, 低磷血症，和高胆红素血症。
药物相互作用
Cabozantinib是CYP3A4底物。强CYP3A4抑制剂的共同给药可能增加cabozantinib暴露。慢性共同给予强CYP3A4诱导剂可能减低cabozantinib暴露。
Cometriq获准用于甲状腺髓样癌患者
近日，美国食品药品管理局(FDA)已批准Cometriq(cabozantinib)治疗进展性、转移性甲状腺髓样癌(MTC)。Cometriq是一种多重受体酪氨酸激酶抑制剂，在正常细胞功能和病理性过程(例如瘤形成、转移、肿瘤血管生成及肿瘤微环境的维持)中均发挥作用。
Cometriq的安全性和有效性在一项纳入330例进展性、转移性MTC患者的国际多中心随机双盲对照试验中得到了检验。入组患者被随机按2:1比例分组，每日1次口服Cometriq 140 mg(n=219)或安慰剂(n=111)，直至发生疾病进展(由负责的医生判断)或出现明显不能耐受的毒性。
与安慰剂组患者相比，Cometriq组患者的无进展生存期(PFS)显著延长，两组的中位PFS分别为4.0个月和11.2个月[危险比(HR)，0.28；95%置信区间(CI)，0.19~0.40；P＜0.0001]。仅在Cometriq组患者中观察到部分应答。Cometriq组患者的中位客观应答持续时间为14.7个月。按照计划进行的中期分析显示，两组在总生存率方面尚未出现显著差异。
研究受试者最常报告的药物不良反应为腹泻、口炎、手足综合征、体重下降、食欲减退、恶心、疲乏、口腔痛、发色改变、味觉障碍、高血压、腹痛和便秘。最常报告的实验室指标异常为肝酶水平升高、淋巴细胞减少、碱性磷酸酶水平升高、低钙血症、中性粒细胞减少、血小板减少、低磷血症和高胆红素血症。
Cometriq的处方信息包含一则加框警告，提醒患者和医务人员警惕潜在的严重甚至致死性胃肠道穿孔和瘘。此外，警示部分也包含了有关发生严重甚至致死性出血的可能性。
Cometriq的推荐剂量为140 mg口服1次/d(1粒80 mg胶囊和3粒20 mg胶囊)。Cometriq不得与食物同服，应告知患者在服用Cometriq之前至少2 h内和之后至少1 h内不要进食
批准日期：2012年11月29日；公司：Exelixis, Inc.
FDA的药物评价和研究中心血液学和肿瘤室主任Richard Pazdur，M.D.说：“在过去2年中Cometriq是第二个被批准治疗甲状腺髓样癌和反映FDA承诺发展和批准为治疗罕见病药物，”“在2011年4月批准Caprelsa，有此罕见和难治疾病患者的治疗选择有限。”本品优先审评。获孤儿药物指定。
Pharmacological Class:
Kinase inhibitor.
Active Ingredient(s):
Cabozantinib 20mg, 80mg; caps.
Company
Exelixis, Inc.
Indication(s):
Treatment of progressive, metastatic medullary thyroid cancer (MTC).
Pharmacology:
Cabozantinib inhibits the tyrosine kinase activity of RET, MET, VEGFR-1, -2 and -3, KIT, TRKB, FLT-3, AXL, and TIE-2. These receptor tyrosine kinases are involved in both normal cellular function and pathologic processes such as oncogenesis, metastasis, tumor angiogenesis, and maintenance of the tumor microenvironment.
Clinical Trials:
The safety and efficacy of Cometriq was assessed in a double-blind, controlled trial of 330 patients. The main efficacy outcome measures were progression-free survival (PFS), objective response (OR), and response duration. A statistically significant prolongation in PFS was demonstrated among Cometriq-treated patients compared to those receiving placebo [HR 0.28 (95% CI: 0.19, 0.40); p <0.0001], with median PFS times of 11.2 months and 4 months in the Cometriq and placebo arms, respectively. Partial responses were observed only among patients in the Cometriq arm (27% vs. 0; p<0.0001). The median duration of objective responses was 14.7 months (95% CI: 11.1, 19.3) for patients treated with Cometriq. There was no statistically significant difference in overall survival between the treatment arms at the planned interim analysis.
Legal Classification:
Rx
Adults:
Swallow whole. 140mg daily. Do not eat at least 2 hours before or 1 hour after dose. Continue until disease progression or unacceptable toxicity. Withhold for Grade 4 hematologic adverse reactions, ≥Grade 3 non-hematologic reactions or intolerable Grade 2 reactions. Upon improvement to Grade 1 or to baseline, reduce dose as follows: previously on 140mg daily, resume at 100mg daily; previously on 100mg daily, resume at 60mg daily; previously on 60mg daily, resume at 60mg if tolerated, otherwise discontinue. Concomitant strong CYP3A4 inhibitor: reduce daily dose by 40mg; resume dose used prior to starting inhibitor 2–3 days after discontinuation of inhibitor. Concomitant strong CYP3A4 inducers: increase daily dose by 40mg; resume dose used prior to starting inducer 2–3 days after discontinuation of inducer. Max daily dose: 180mg.
Children:
Not studied.
Warnings/Precautions:
Permanently discontinue if the following occurs: GI or non-GI perforation/fistula formation, severe hemorrhage, serious arterial thromboembolic events (eg, MI, cerebral infarction), nephrotic syndrome, malignant hypertension, hypertensive crisis, persistent uncontrolled hypertension despite optimal medical management, osteonecrosis of the jaw, reversible posterior leukoencephalopathy syndrome. Moderate-to-severe hepatic impairment: not recommended. Recent history of hemorrhage, hemoptysis: avoid. Stop treatment at least 28 days prior to scheduled surgery (including invasive dental procedures); withhold dose if dehiscence or wound healing complications require medical intervention. Monitor for bleeding, hypertension, proteinuria (measure urine protein regularly). Use effective contraception during and up to 4 months after completion of therapy. Pregnancy (Cat. D). Nursing mothers: not recommended.
Interaction(s)
Avoid concomitant strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole, grapefruit or grapefruit juice) and strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort): see Adult dose.
Adverse Reaction(s)
Diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome, decreased weight/appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, constipation, increased AST, ALT, alkaline phosphatase, lymphopenia, hypocalcemia, neutropenia, thrombocytopenia, hypophosphatemia, hyperbilirubinemia.
How Supplied:
140mg daily-dose carton—4 blister cards (each: 7x80mg and 21x20mg caps); 100mg daily-dose carton—4 blister cards (each: 7x80mg and 7x20mg caps); 60mg daily-dose carton—4 blister cards (each: 21x20mg caps)
LAST UPDATED:
1/18/2013
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注：以下产品不同规格和不同价格，详细情况以咨询为准！
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产地国家: 美国
原产地英文商品名:
Cometriq 100mg 14caps
原产地英文药品名:
CABOZANTINIB S-MALATE
中文参考商品译名:
Cometriq 100mg 14caps
中文参考药品译名:
CABOZANTINIB S-MALATE
生产厂家中文参考译名:
EXELIXIS (US).
生产厂家英文名:
EXELIXIS (US).
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原产地英文商品名:
Cometriq 60mg 21caps
原产地英文药品名:
CABOZANTINIB S-MALATE
中文参考商品译名:
Cometriq 60mg 21caps
中文参考药品译名:
CABOZANTINIB S-MALATE
生产厂家中文参考译名:
EXELIXIS (US).
生产厂家英文名:
EXELIXIS (US).
该药品相关信息网址1:
http://www.cometriq.com/
该药品相关信息网址2:
http://www.drugs.com/mtm/cometriq.html