新类药片Cabometyx(cabozantinib 中文药名：卡赞替尼片)-为治疗肾细胞癌
近日，美国食品和药物管理局FDA批准Cabometyx（cabozantinib）药片的病人谁也接受过抗血管生成治疗晚期肾细胞癌（RCC）的治疗。碾压是在成人肾脏癌的最常见形式。
Cabometyx这是由美国食品药品管理局授予的快速审批和突破疗法名称，是在3期临床试验以证明病人在所有三个主要疗效参数晚期肾细胞癌，强大和临床意义的改善第一疗法 - 总生存率，无进展生存和客观缓解率。
可促进肿瘤血管生成（血管生长），生长，侵袭和metastasis.6-9 MET和AXL也可以提供驱动阻力VEGF受体inhibitors.5,6逃生途径。
关于Cabometyx
Cabometyx靶包括MET，AXL和VEGFR-1，-2和-3。在临床前模型，cabozantinib已经显示出抑制这些受体，它参与正常细胞功能和病理过程，例如肿瘤血管生成，侵入，转移和耐药性的活性。
Cabometyx（cabozantinib）的片剂制剂，将20毫克，40毫克或60毫克剂量的可用。推荐的剂量为60毫克口服，每日一次。
批准日期：2016年4月25日；公司：Exelixis，Inc.
CABOMETYX™(卡赞替尼 cabozantinib)片，供口服使用
美国初始批准：2012
作用机制
体外生化和/或细胞学分析曽显示卡赞替尼抑制MET，VEGFR-1，-2和-3，AXL，RET，ROS1，TYRO3，MER，KIT，TRKB，FLT-3，和TIE-2酪氨酸激酶的活性。这些受体酪氨酸激酶是涉及正常细胞学功能和病理学过程两个方面例如肿瘤发生，转移，肿瘤血管生成，药物抗性，和肿瘤慰环境的维持。
适应证和用途
CABOMETYX是一个激酶抑制剂适用为有晚期肾细胞癌(RCC)曽接受以前抗血管生成治疗患者的治疗。
剂量和给药方法
⑴ 推荐剂量：60mg口服，每天1次。
⑵ 指导患者服用CABOMETYX前和后至少1小时不要吃共至少2小时。
⑶ 不要用卡赞替尼胶囊替代CABOMETYX片。
剂型和规格
20mg，40mg，和60mg片。
禁忌证
无。
警告和注意事项
⑴ 出血：如最近严重出血病史不要给予CABOMETYX。
⑵ GI穿孔和瘘管：监视症状。对不能适当地处理或穿孔的瘘管终止。
⑶ 血栓性事件：对心肌梗死，脑梗塞，或其他严重动脉血栓栓塞事件终止CABOMETYX。
⑷高血压和高血压危象：定期地监视血压。对不能用抗高血压治疗控制高血压危象或严重高血压终止CABOMETYX。
⑸ 腹泻：可能是严重。立即中断CABOMETYX治疗直至腹泻解决或减轻至1级。推荐标准抗治疗。
⑹ 掌跖红感觉迟钝综合征(PPES)：中断CABOMETYX治疗直至PPES解决或减轻至1级，
⑺ 可逆性后部白质脑病综合征(RPLS)：终止CABOMETYX。
⑻ 胚胎-胎儿毒性：可致胎儿危害。忠告生殖潜能女性对胎儿潜在风险和使用有效避孕。
不良反应
最常报道的(≥ 25%)不良反应为：腹泻，疲乏，恶心，食欲减退，掌跖红感觉迟钝综合征(PPES)，高血压，呕吐，体重减低，和便秘。
报告怀疑不良反应，联系Exelixis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
强CYP3A4抑制剂：减低CABOMETYX剂量。
特殊人群中使用
⑴ 轻度至中度肝受损：减低CABOMETYX剂量。
⑵ 哺乳：当服用CABOMETYX时忠告不要哺乳喂养。
如何供应/贮存和处置
CABOMETYX片被供应如下:
60 mg片是黄色薄膜包衣，椭圆形无划线，在片一侧凹有“XL”和另一侧“60”；可得到30片瓶：NDC 42388-023-26
40 mg片是黄色薄膜包衣，三角形无划线，在片一侧凹有“XL”和另一侧“40”；可得到30片瓶：NDC 42388-025-26
20 mg片是黄色薄膜包衣，圆形无划线，在片一侧凹有“XL”和另一侧“20”；可得到30片瓶：NDC 42388-024-26
贮存CABOMETYX在20°C至25°C(68°F至77°F)；外出允许从15°C至30°C(59°F至86°F)[见USP控制室温]。
Cabometyx (Cabozantinib Tablets)
General Information
Cabometyx (cabozantinib) is a kinase inhibitor.
Cabometyx is specifically indicated for the treatment of patients with advanced renal cell carcinoma who have received prior antiangiogenic therapy.
Cabometyx is supplied as tablets for oral administration The recommended dose is 60 mg orally, once daily. Patients should not to eat for at least 2 hours before and at least 1 hour after taking Cabometyx. Do not substitute Cabometyx tablets with cabozantinib capsules.
CABOMETYX™ (cabozantinib) is indicated for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior anti-angiogenic therapy.
Important Safety Information
Hemorrhage: Severe hemorrhage occurred with CABOMETYX™. The incidence of Grade ≥3 hemorrhagic events was 2.1% in CABOMETYX-treated patients and 1.6% in everolimus-treated patients. Fatal hemorrhages also occurred in the cabozantinib clinical program. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: Fistulas were reported in 1.2% (including 0.6% anal fistula) of CABOMETYX-treated patients and 0% of everolimus-treated patients. GI perforations were reported in 0.9% of CABOMETYX-treated patients and 0.6% of everolimus-treated patients. Fatal perforations occurred in the cabozantinib clinical program. Monitor patients for symptoms of fistulas and perforations. Discontinue CABOMETYX in patients who experience a fistula that cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. Venous thromboembolism was reported in 7.3% of CABOMETYX-treated patients and 2.5% of everolimus-treated patients. Pulmonary embolism occurred in 3.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Events of arterial thromboembolism were reported in 0.9% of CABOMETYX-treated patients and 0.3% of everolimus-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension. Hypertension was reported in 37% (15% Grade ≥3) of CABOMETYX-treated patients and 7.1% (3.1% Grade ≥3) of everolimus-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: Diarrhea occurred in 74% of patients treated with CABOMETYX and in 28% of patients treated with everolimus. Grade 3 diarrhea occurred in 11% of CABOMETYX-treated patients and in 2% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to diarrhea occurred in 26% of patients.
Palmar-Plantar Erythrodysesthesia Syndrome (PPES): PPES occurred in 42% of patients treated with CABOMETYX and in 6% of patients treated with everolimus. Grade 3 PPES occurred in 8.2% of CABOMETYX-treated patients and in <1% of everolimus-treated patients. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPES or Grade 3 PPES until improvement to Grade 1; resume CABOMETYX at a reduced dose. Dose modification due to PPES occurred in 16% of patients.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS, a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion, or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity: CABOMETYX can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, PPES, hypertension, vomiting, weight decreased, and constipation.
Drug Interactions: Strong CYP3A4 inhibitors and inducers: Reduce the dosage of CABOMETYX if concomitant use with strong CYP3A4 inhibitors cannot be avoided. Increase the dosage of CABOMETYX if concomitant use with strong CYP3A4 inducers cannot be avoided.
Lactation: Advise a lactating woman not to breastfeed during treatment with CABOMETYX and for 4 months after the final dose.
Reproductive Potential: Contraception―Advise females of reproductive potential to use effective contraception during treatment with CABOMETYX and for 4 months after the final dose. Infertility―CABOMETYX may impair fertility in females and males of reproductive potential.
Hepatic Impairment: Reduce the CABOMETYX dose in patients with mild (Child-Pugh score [C-P] A) or moderate (C-P B) hepatic impairment. CABOMETYX is not recommended for use in patients with severe hepatic impairment.

完整使用资料附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3850cce2-6137-42e5-a792-d318c4a4b3b5
Exelixis公司口服抗癌药CABOMETYX(CABOZANTINIB S-MALATE)TABLET ORAL再获欧盟批准上市，为肾癌二线治疗新选择
继今年4月获得美国食品和药物管理局（FDA）批准治疗晚期肾细胞癌（RCC）之后，Exelixis制药公司的口服抗癌药Cabometyx（cabozantinib）近日再获欧盟批准，用于前一次治疗为血管内皮生长因子（VEGF）靶向疗法治疗失败的晚期肾细胞癌。
在欧盟，Cabometyx通过加速审批程序获批，该药是首个在III期临床中在全部3个关键疗效参数方面（总生存期，OS；无进展生存期，PFS；客观缓解率，ORR）均实现强劲的临床意义改善的创新药物。Cabometyx的上市，将为欧洲的晚期肾细胞癌群体提供一种新的二线治疗选择。
Cabometyx的获批，是基于开放标签、事件驱动、大型、随机III期临床研究METEOR的数据。该研究在658例既往接受过至少一次VEGFR-TKI（血管生长因子受体-酪氨酸激酶抑制剂）靶向疗法治疗失败的晚期肾细胞癌（RCC）患者中开展，评估了Cabometyx相对于诺华口服靶向抗癌药Afinitor（everolimus，依维莫司）的疗效和安全性。
数据显示，与Afinitor治疗组相比，Cabometyx治疗组无进展生存期（中位PFS：7.4个月 vs 3.8个月）显著延长，疾病进展或死亡风险显著降低42%。同时，与Afinitor治疗组相比，Cabometyx治疗组客观缓解率（ORR）也得到了统计学意义的显著提高（研究员评估的ORR：24% vs 4%，p＜0.0001；中央审查的ORR：17% vs 3%，p＜0.0001）。此外，与Afinitor治疗组相比，Cabometyx治疗组总生存期（中位OS：21.4个月 vs 16.5个月，p=0.0003）也得到了统计学意义和临床意义的显著改善，死亡率下降34%。
在欧盟，cabozantinib之前已获批用于进行性不可切除性局部晚期或转移性甲状腺髓样癌（medullary thyroid carcinoma，MTC）成人患者的治疗，其品牌名为Cometriq。
今年3月，法国制药公司Ipsen与Exelixis达成了一笔8.55亿美元的协议，获得了cabozantinib在除美国、加拿大、日本以外地区的商业化权利。此次cabozantinib获得欧盟批准治疗晚期肾细胞癌。