色瑞替尼（ceritinib）

色瑞替尼（ceritinib）由Novartis Pharms公司研究与开发,于2014年4月29日经美国食品药品监督管理局（FDA）批准上市,商品名为Zykadia^TM,该药为胶囊剂。用于对crizotinib（克唑替尼）治疗后已进展或不能耐受的晚期间变性淋巴瘤激酶阳性（Anaplastic lymphoma kinasepositive,ALK^＋）转移性非小细胞肺癌（NSCLC）患者的治疗。推荐剂量为每天750mg。     

艾乐替尼盐酸盐

2015年12月11日,美国FDA批准罗氏公司研制的口服抗肺癌新药艾乐替尼盐酸盐(alectinib hydrochloride,商品名Alecensa)上市,用于治疗ALK基因突变的晚期(转移性)非小细胞肺癌。该药物适用于对克唑替尼治疗后(或因不能耐受)出现复发的患者。艾乐替尼盐酸盐是美国FDA批准的第三个用于治疗ALK基因突变的晚期(转移性)非小细胞肺癌的药物[1]。     

吉非替尼片剂

吉非替尼(Gefitinib)即合成的苯胺喹唑啉[4-(3，氯-4-氟苯胺)-7-甲氧基-6-(3-异构亚丙氧基)喹唑啉]o该药是一种选择性表皮生长因子受体(EGFR)阻断剂／酪氨酸激酶抑制剂，可用于治疗非小细胞肺癌。目前尚未有临床资料证实该药可显著延长患者生存时间。该药商品名为易瑞沙(Iressa)，由阿斯利康公     

色瑞替尼治疗间变性淋巴瘤激酶阳性非小细胞肺癌的研究概况

目的:综述色瑞替尼治疗间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌(NSCLC)的研究概况。方法:以"非小细胞肺癌""间变性淋巴瘤激酶抑制剂""色瑞替尼""Non-small cell lung cancer""Ceritinib"作为关键词,查阅中国知网、Pub Med数据库截止至2017年6月的文献,就色瑞替尼治疗ALK阳性NSCLC的药效学、药动学、临床疗效、安全性等的研究进行整理分析和归纳总结。结果与结论:共检索到英文文献1 464篇,中文文献127篇,其中有效文献27篇。色瑞替尼为ALK的高效抑制剂,能有效克服第一代ALK克唑替尼的部分耐药突变;其多次给药后呈非线性药动学特征,不建议与细胞色素P4503A的强抑制剂和诱导剂联用。与化疗和克唑替尼比较,色瑞替尼显著延长了患者的中位无进展生存期与总生存期,其透过颅内浓度高于克唑替尼;最常报道的不良事件是腹泻、恶心、呕吐、腹痛和食欲下降,通常为1~2级,可通过降低剂量减少不良事件的发生,较少引起治疗中止。色瑞替尼可作为ALK阳性、经克唑替尼治疗后疾病进展或不能耐受的晚期NSCLC患者的治疗方案。     

美国食品药品监督管理局批准色瑞替尼胶囊治疗ALK＋非小细胞肺癌

诺华公司色瑞替尼胶囊治疗ALK酪氨酸激酶受体阳性（ ALK＋）转移性非小细胞肺癌（ NSCLC）患者（克唑替尼治疗时进展或无法耐受）获得了美国食品药品监督管理局（ FDA）批准。对163例克唑替尼治疗时疾病进展或不能耐受其治疗的转移性ALK＋ NSCLC患者实施的关键性研究中,复治患者的总缓解率是54.6%,缓解持续时间中位数是7.4个月。发生率至少为25%的不良事件包括腹泻、恶心、转氨酶升高、呕吐、腹痛、疲劳、食欲减退及便秘。     

非小细胞肺癌治疗药埃罗替尼(erlotinib)

1商品名Tarceva2开发与上市厂商本品由OSI制药公司研制,于2004年11月在美国首次上市,2005年3月在欧洲上市。3适应证用于治疗至少1次化疗失败的局限性晚期或转移性非小细胞肺癌(NSCLC)。4药理作用本品可抑制细胞内以及与表皮生长因子受体(EGFR)有关的酪氨酸激酶的磷酸化作用。本     

盐酸厄洛替尼

[通用名称]erlotinib hydrochloride tablets，盐酸厄洛替尼片     

吉非替尼治疗晚期非小细胞肺癌126例

目的 观察吉非替尼治疗晚期非小细胞肺癌(NSCLC)的临床疗效.方法 126例晚期NSCLC患者口服吉非替尼,至不可耐受时停药.结果 总有效率为30.1%,疾病控制率为81.7%.有效患者的中位缓解时间为6.6个月,全组的中位肿瘤进展时间为4.9个月,中位总生存时间为9.8个月,1年生存率为38.2%.腺癌患者的有效率、生存时间及TIP均显著高于鳞癌患者,女性患者的有效率和生存时间优于男性患者.脑转移患者的有效率为50%.主要不良反应为皮疹和腹泻,多数较轻并可逆.结论 吉非替尼治疗晚期NSCLC安全有效,易为患者接受.     

阿帕替尼治疗晚期非小细胞肺癌1例

<正>1临床资料患者女性,49岁,2012年3月以"咳嗽、咳痰2月余"为主诉就诊。一般情况:PS 1分,身高158 cm,体质量48 kg。无高血压、冠心病、糖尿病史,无肿瘤家族史,无吸烟、饮酒史。辅助检查:胸部CT:右肺下叶周围型肺癌,并两肺多发转移。进一步做纤维支气管镜:(右下肺基底段钳检)低分化鳞状细胞癌。诊断:右下肺低分化鳞癌T4N3M1Ⅳa期。治疗过程:患者肿瘤Ⅳ期,无手术指征。于2012年3月31日至7月     

基于美国FAERS数据库的塞瑞替尼不良事件信号挖掘研究

目的 挖掘和分析塞瑞替尼相关不良事件信号,为临床安全合理使用塞瑞替尼提供参考与指导.方法 利用比例失衡法和综合标准法(MHRA)对美国FDA不良事件报告系统(FAERS)中2015年第一季度至2020年第二季度共22个季度的塞瑞替尼相关不良事件报告进行数据挖掘和分析.结果 获得以塞瑞替尼为首要怀疑药物的不良事件报告总数...     

Comparative efficacy of brigatinib versus ceritinib and alectinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small cell lung cancer

Objective: Brigatinib, ceritinib, and alectinib are approved to treat crizotinib-refractory anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), but no trial has compared them head-to-head. A matching-adjusted indirect comparison (MAIC) was conducted to estimate the relative efficacy of these agents in the crizotinib-refractory setting.

Methods: MAIC is a propensity score-type method that adjusts for differences in baseline characteristics between trials to estimate relative efficacy. Analyses were based on patient-level data from the ALTA trial for brigatinib and published summary-level trial data from ASCEND-1 and ASCEND-2 for ceritinib and NP28761 and NP28673 for alectinib. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared.

Results: After matching, all key baseline characteristics were balanced between trials. Compared with ceritinib, brigatinib was associated with longer PFS (ASCEND-1: median 15.7 vs 6.9 months, hazard ratio (HR) [95% confidence interval]?=?0.38 [0.26–0.57]; ASCEND-2: median?=?18.3 vs 7.2 months, HR?=?0.33 [0.20–0.56]) and OS (ASCEND-1: not available; ASCEND-2: median 27.6 vs 14.9 months, HR?=?0.33 [0.17–0.63]). Versus alectinib, brigatinib was associated with longer PFS (NP28761: median?=?17.6 vs 8.2 months, HR?=?0.56 [0.36–0.86]; NP28673: median?=?17.6 vs 8.9 months, HR?=?0.61 [0.40–0.93]); results for OS were inconclusive (NP28761: median?=?27.6 vs 22.7 months, HR?=?0.70 [0.42–1.16]; NP28673: median?=?27.6 vs 26.0 months, HR?=?0.66 [0.39–1.09]). ORR was similar.

Conclusion: In crizotinib-refractory ALK?+?NSCLC patients, relative efficacy estimates suggest brigatinib may have prolonged PFS and OS vs ceritinib and prolonged PFS vs alectinib.     

Comparative efficacy of first-line ceritinib and crizotinib in advanced or metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer: an adjusted indirect comparison with external controls

Objective: In the absence of head-to-head trials, this study indirectly compared progression free survival (PFS) and overall survival (OS) between ceritinib and crizotinib among patients with previously untreated advanced anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

Methods: A matching-adjusted indirect comparison method was implemented to adjust for cross-trial differences in patient characteristics between ASCEND-4 and PROFILE 1014 trials. Patient-level data from ASCEND-4 and published summary data from PROFILE 1014 were used. Patients in ASCEND-4 were reweighted to match average baseline characteristics (i.e. age, sex, race, tumor histology, ECOG score, smoking status, extent of disease, and presence of brain metastases) reported for PROFILE 1014 patients using propensity score weighting. PFS and OS were then compared between balanced populations.

Results: ASCEND-4 included more current smokers (8.0% vs 4.4%) and fewer patients under the age of 65 years (78.5% vs 84.0%) compared to PROFILE 1014. After matching, these and all other patient characteristics were balanced between the two trial populations. Compared to crizotinib, ceritinib was associated with a significantly longer PFS (hazard ratio [95% confidence interval] (HR [CI])?=?0.64 [0.47–0.87]; median PFS: 25.2 vs 10.8 months, log-rank p-value?=?0.003). OS did not differ significantly, with a HR of 0.82 [0.54–1.27] for ceritinib compared to crizotinib.

Conclusions: In the adjusted indirect comparison with external controls, the second generation ALK inhibitor, ceritinib, was associated with a significantly prolonged PFS compared to crizotinib as first-line treatment for ALK-positive NSCLC.     

Selective and robust UPLC-MS/MS method for simultaneous quantitative determination of anlotinib,ceritinib and ibrutinib in rat plasma and its application to pharmacokinetic study

OBJECTIVE A selective and robust ultrahigh performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS) method has been firstly developed for the simultaneous determination of three nextgeneration anti-tumor tyrosine kinase inhibitors(anlotinib,ANL; ceritinib, CER; ibrutinib, IBR) in rat plasma using cost-effective protein precipitation extraction. METHODS and RESULTS LC separation was achieved on Waters XBrige C18 column(50 mm×2.1 mm, 3.5 μm) under gradient conditions in a run time of 5 min. Electrospray ionization in the positive ion mode was involved through mass spectrometry. Multiple reaction monitoring(MRM) transitions were at m/z 408.2→339.2 for ANL, 558.2→433.2 for CER, 441.0→138.0 for IBR, 285.0→193.1 for diazepam(internal standard), respectively. The optimized method was validated based on US FDA guideline, EMEA guideline as well as Pharmacopoeia of the People′s Republic of China. The assay was linear in the range of 0.1-20 μg·L~(-1) for ANL, 2-1000 μg·L~(-1) for CER, 1-500 μg·L~(-1) for IBR. Intraand inter-day accuracy and precision for all analytes were ≦ 13.84% and ≦ 12.56%, respectively. ANL, CER and IBR were sufficiently stable under most investigated conditions. The optimized method was successful y applied for a pharmacokinetic study after single oral gavage administration of mixture(ANL, CER and IBR) at dose of 6, 25 and 10 mg·kg~(-1). CONCLUSION The proposed analytical assay demonstrates great improvements in respect of previous methods reported in literatures, such as costeffective sample preparation, short chromatographic time, smaller amount of sample(50 μL), satisfied extraction recovery and matrix effect.