Inlyta (阿西替尼axitinib)-晚期肾细胞癌新药

批准时间：2012年1月27日

制造商：
辉瑞公司

类药物：
激酶抑制剂。

活性成分（S）：
阿西替尼1毫克，5毫克;标签。
指示（S）：
一个事先全身治疗失败后的晚期肾细胞癌（RCC）治疗。

药理作用：
阿西替尼已被证明能够抑​​制受体酪氨酸激酶，包括血管内皮生长因子受体（VEGFR）-1，VEGFR-2，VEGFR-3在治疗血药浓度。这些受体被牵连在病理的血管生成，肿瘤的生长，癌症的发展。

临床试验：
在一个开放标签，多中心第三期研究评估的安全性和疗效Inlyta。共有723例晚期肾癌的疾病或治疗后1前全身治疗，包括舒尼替尼，贝伐单抗，temsirolimus的，或含有细胞因子治疗进展，随机（1:1）接收Inlyta（n = 361）或索拉非尼组（n = 362）。无进展生存期（PFS）进行了评估盲的独立的中央审查委员会。其他终点包括客观缓解率（ORR）和总生存（OS）。

有终点的PFS（6.7个月Inlyta对索拉非尼为4.7个月，HR = 0.67（0.54，0.81），P <0.0001）索拉非尼为Inlyta统计学显着的优势。在OS之间的武器也没有统计学显着性差异。

法律分类：
RX

成人：
除了12小时。一杯水吞下整。最初5毫克，每天两次。如果至少连续两个星期没有不良反应> 2级，血压正常，并没有接受抗高血压药物的耐受性，可能会增加剂量以7MG，每天两次，然后10毫克，每天两次。可能会减少5毫克，每天两次到3mg剂量，每日两次，然后2毫克，每天两次，如果需要额外的剂量减少。伴随强CYP3A4 / 5抑制剂：避免如有必要，减少约为Inlyta剂量半。如果停止强CYP3A4 / 5抑制剂，剂量Inlyta（3-5半衰期抑制剂）后返回之前使用效CYP3A4 / 5抑制剂开始。中度肝功能损害：减少约半剂量。

儿童：
没有研究过。

警告/注意事项：
控制和监测的BP前和治疗期间，停止（尽管降压治疗和剂量减少），如果严重和持久性高血压。血栓事件的风险。未经治疗的脑转移瘤，最近活跃的消化道出血：不建议。中断治疗，如果出血需要医疗干预。胃肠穿孔及瘘管形成;显示器。监视开始治疗前，甲状腺，肝功能（ALT，AST，胆红素），蛋白尿，然后定期。减少剂量或暂时中断为中度至重度蛋白尿。可逆性后部白质脑病综合征（永久终止，如果发生）的风险。停止治疗至少24小时前预定手术。严重肝功能损害。终末期肾脏疾病。怀孕（目录四）;避免。在治疗过程中使用适当的避孕。哺乳母亲：不推荐。

互动（补）：
见成人剂量。避免强CYP3A4 / 5抑制剂（如葡萄柚汁，酮康唑，伊曲康唑，克拉霉素，阿扎那韦，茚地那韦，奈法唑酮，奈非那韦，利托那韦，沙奎那韦，泰利霉素，伏立康唑），CYP3A4 / 5的诱导剂（如利福平，地塞米松，苯妥英，卡马西平，利福布丁，rifapentin，苯巴比妥，圣约翰草），中度CYP3A4 / 5诱导剂（例如，波生坦，依非韦伦，etravirine的，莫达非尼，奈夫西林）。

不良反应（S）：
高血压，胃肠不适，乏力，食欲下降，发音障碍，手掌，足底红肿（手足）综合征，体重下降，乏力，便秘。

如何提供：
标签1毫克，180 5毫克，60;

FDA批准Inlyta (阿西替尼axitinib)用于治疗晚期肾细胞癌

2012年1月27日，美国食品药品监督管理局批准Inlyta (阿西替尼)用于治疗其他药物治疗无效的晚期肾癌（肾细胞癌）。
肾细胞癌是肾癌的一种，始于肾小管内层。Inlyta是一日服用两次的片剂，通过阻断激酶蛋白起到抑制肿块生长和癌症进展。
对723名经前期系统治疗但在治疗期或治疗后疾病仍有进展的患者，进行随机、无盲、多中心临床试验评估了该药的安全性和有效性。研究衡量患者无进展生存时间，结果显示：与标准治疗（索拉非尼）4.7个月的中位无进展存活期相比，Inlyta的中位无进展存活期为6.7个月。
在临床研究中观察到的最常见（大于20%的患者）副作用为腹泻、高血压、疲劳、食欲减退、恶心、失音（言语困难）、手-足综合征、体重减轻、呕吐、虚弱和便秘。
高血压患者在服用Inlyta前应加以良好控制。一些患者在服用Inlyta后出现了出血问题，这在一些病例中是致命的。未经治疗的脑瘤或胃肠道出血患者不应服用Inlyta。

INLYTA (axitinib) 1mg, 5mg tablets by Pfizer
RELATED CONDITIONSBladder, kidney, and other urologic cancers  Pfizer announced that the FDA has approved Inlyta (axitinib) for the treatment of patients with advanced renal cell carcinoma who have not responded to another drug for this type of cancer. This approval was based on data from a randomized, open-label, multicenter clinical study of 723 patients whose disease had progressed on or after treatment with one prior systemic therapy. The primary efficacy endpoint of the study was progression-free survival (PFS). Results showed a median PFS of 6.7 months compared with 4.7 months with a standard treatment (sorafenib).

Axitinib is an oral and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2 and 3, receptors that can influence tumor growth, vascular angiogenesis and progression of cancer (the spread of tumors).

INLYTA

Indication(s):

Treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

Pharmacology:

Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression.

Clinical Trials:

The safety and efficacy of Inlyta were evaluated in an open-label, multicenter Phase 3 study. A total of 723 patients with advanced RCC whose disease had progressed on or after treatment with 1 prior systemic therapy, including sunitinib-, bevacizumab-, temsirolimus-, or cytokine-containing regimens were randomized (1:1) to receive Inlyta (N=361) or sorafenib (N=362). Progression-free survival (PFS) was assessed by a blinded independent central review committee. Other endpoints included objective response rate (ORR) and overall survival (OS).

There was a statistically significant advantage for Inlyta over sorafenib for the endpoint of PFS (6.7 months for Inlyta vs. 4.7 months for sorafenib; HR=0.67 (0.54, 0.81); P<0.0001). There was no statistically significant difference between the arms in OS.

Legal Classification:

Rx

Adults:

Take 12 hours apart. Swallow whole with a glass of water. Initially 5mg twice daily. If tolerated for at least two consecutive weeks with no adverse reactions >Grade 2, normotensive, and not receiving antihypertensives, may increase dose to 7mg twice daily, then 10mg twice daily. May reduce dose from 5mg twice daily to 3mg twice daily, then 2mg twice daily if additional dose reduction required. Concomitant strong CYP3A4/5 inhibitors: avoid; if warranted, decrease Inlyta dose by approximately ½. If strong CYP3A4/5 inhibitor discontinued, return Inlyta dose (after 3–5 half-lives of the inhibitor) to that used prior to CYP3A4/5 inhibitor initiation. Moderate hepatic impairment: decrease dose by approximately ½.

Children:

Not studied.

Warnings/Precautions:

Control and monitor BP prior to and during therapy; discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction). Risk of thromboembolic events. Untreated brain metastasis, recent active GI bleed: not recommended. Interrupt therapy if bleeding requires medical intervention. GI perforation and fistula formation; monitor. Monitor thyroid, liver function (ALT, AST, bilirubin), and for proteinuria before starting therapy, then periodically. Reduce dose or temporarily interrupt for moderate to severe proteinuria. Risk of reversible posterior leukoencephalopathy syndrome (permanently discontinue if occurs). Stop treatment at least 24hrs prior to scheduled surgery. Severe hepatic impairment. End-stage renal disease. Pregnancy (Cat. D); avoid. Use adequate contraception during therapy. Nursing mothers: not recommended.

Interaction(s):

See Adult dose. Avoid strong CYP3A4/5 inhibitors (eg, grapefruit juice, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole), CYP3A4/5 inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, St. John’s wort), moderate CYP3A4/5 inducers (eg, bosentan, efavirenz, etravirine, modafinil, nafcillin).

Adverse Reaction(s):

GI upset, hypertension, fatigue, decreased appetite, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, asthenia, constipation.

How Supplied:

Tabs 1mg—180; 5mg—60

Last Updated:

3/26/2012