英文药名：Cometriq(cabozantinib)capsules 中文药名：卡博替尼胶囊 生产厂家：Exelixis Inc公司 药品介绍 2012年11月29日美国食品药品监督管理局(FDA)批准Cometriq(cabozantinib)治疗已播散至身体其他部分(转移的)甲状腺髓样癌。 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。 美国初次批准：2012 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 20mg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。 为报告怀疑不良反应，联系Exelixis，Inc.公司电话1-855-500-3935或FDA电话1-800-FDA-1088或www.fda.gov/medwatch. 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 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 2012年11月29日美国食品药品监督管理局(FDA)批准Cometriq(cabozantinib)治疗已播散至身体其他部分(转移的)甲状腺髓样癌。 甲状腺制造一种有助于维持血中钙健康水平的激素被称为降钙素[calcitonin]细胞中发生甲状腺髓样癌。这性癌自发发生或在有某些基因突变家族，导致内分泌系统1种或更多癌症，包括甲状腺。 美国国立癌症研究所估计在2012年56,460 美国人将诊断有甲状腺癌和1,780将死于此病。约4%甲状腺癌是甲状腺髓癌，为罕见甲状腺癌之一。 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。” 美国FDA在其优先审评程序下在6个月内完成Cometriq的申请审评。这个程序为可能提供治疗重要进展或当前没有治疗存在的药物提供一个加快6个月审评。Cometriq因为意向治疗罕见病或情况还获得孤儿产品指定。 Cometriq是激酶抑制剂阻断涉及髓样癌细胞的发育和生长的异常激酶蛋白。在服用Cometriq前至少2小时和后1小时患者不应进食。 在一项涉及330例有甲状腺髓样癌患者临床研究确定Cometriq的安全性和有效性。用Cometriq治疗增加无癌进展生存患者生存时间长度(无进展生存) 而，有些患者，肿瘤大小减小(缓解率)。 被给予Cometriq患者无肿瘤生长生存平均11.2个月与之比较接受糖丸(安慰剂)患者平均4个月。结果还显示用Cometriq治疗患者27%肿瘤大小减小平均持续接近15个月，而who 接受安慰剂患者未见减小。用Cometriq治疗不延长 患者生命。 Cometriq处方资料包括黑框警告警告患者和卫生保健专业人员严重和在有些患者中结肠内发生致命性出血和孔(穿孔和瘘管)。 最常见副作用是腹泻；炎症或口腔痛；发红，疼痛，或指趾肿胀(手足综合征)；体重减轻；食欲不振；恶心；疲乏；口疼；头发灰或色消失；难闻味；高血压新发作或恶化；腹痛和便秘。最常见实验室异常包括肝酶增加，低钙和磷，白血细胞和血小板减低。 Cometriq由Exelixis上市，位于南旧金山，加州。Caprelsa (vandetanib)由Wilmington，Del.-based AstraZeneca药业上市。.