厄洛替尼

厄洛替尼
临床资料
商品名（英语：Drug nomenclature）	Tarceva
其他名称	Erlotinib hydrochloride
AHFS/Drugs.com	Monograph
MedlinePlus	a605008
核准状况	美 DailyMed: Erlotinib;
怀孕分级	澳: C ; ;
给药途径	口服给药
ATC码	L01EB02 (WHO) ;
法律规范状态
法律规范	澳：限医生处方（S4）; 英：处方药（℞-only） (POM); 美：处方药（℞-only）;
药物动力学数据
生物利用度	59%
血浆蛋白结合率	95%
药物代谢	肝脏 (主要经由CYP3A4, 小量经由CYP1A2)
生物半衰期	36.2小时 (中位数)
排泄途径	>98%化为代谢物, 代谢物中 >90%经由粪便移除, 9%经由尿液移除
识别信息
	IUPAC命名法 N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy); quinazolin-4-amine; ; ;
CAS号	183321-74-6
PubChem CID	176870;
IUPHAR/BPS	4920;
DrugBank	DB00530 ;
ChemSpider	154044 ;
UNII	J4T82NDH7E;
KEGG	D07907 ;
ChEBI	CHEBI:114785 ;
ChEMBL	ChEMBL553 ;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID8046454 ;
ECHA InfoCard	100.216.020
化学信息
化学式	C22H23N3O4
摩尔质量	393.44 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	SMILES COCCOc1cc2c(cc1OCCOC)ncnc2Nc3cccc(c3)C#C;
	InChI InChI=1S/C22H23N3O4/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25) ; Key:AAKJLRGGTJKAMG-UHFFFAOYSA-N ;

厄洛替尼（英语：erlotinib）以Tarceva（中文译名"得舒缓"或"特罗凯"）等品牌于市面销售，是一种用于治疗非小细胞肺癌（英语：non-small-cell lung cancer）（NSCLC）和胰脏癌的药物。^[4]具体而言，它用于治疗表皮生长因子受体(EGFR) 发生突变（外显子19缺失(del19) 或外显子21 (L858R) 替换突变）的非小细胞肺癌，且癌细胞已扩散到身体其他部位。^[4]厄洛替尼经由口服方式给药。^[4]

Quick Facts 临床资料, 商品名（英语：Drug nomenclature） ...

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使用此药物的常见副作用有皮疹、腹泻、肌肉痛、关节痛和咳嗽。^[4]^[3]严重的副作用有肺部问题、肾脏问题、肝衰竭、肠胃穿孔、中风和角膜溃疡（英语：corneal ulceration）。^[4]个体于怀孕期间使用可能会伤害胎儿。^[4]它是一种酪胺酸激酶抑制剂，透过抑制表皮生长因子受体而发挥作用。^[4]

厄洛替尼于2004年获得美国食品药物管理局（FDA）批准得用于医疗用途。^[5]^[4]^[3]它已列入世界卫生组织基本药物标准清单之中。^[6]市面上已有此药物的通用名药物流通。^[7]

肺癌

厄洛替尼联合化疗以治疗不可切除的非小细胞肺癌时，比单独采用化疗的总存活期提高19%，而在无恶化存活期（英语：progression-free survival）(PFS) 则提高29%。^[8]^[9]^[10]FDA的批准是使用此药物治疗至少一种先前化疗方案失败的局部晚期或是转移性非小细胞肺癌。^[11]

厄洛替尼已被证明对有，或是没有表皮生长因子突变的肺癌患者均有效，但似乎对有突变的患者更为有效。^[12]^[13]总存活期、无恶化存活期和一年存活期与标准二线治疗药物（欧洲紫杉醇或培美曲塞（英语：pemetrexed））相似。整体缓解率比标准二线化疗好约50%。^[13]患有腺癌或细支气管肺泡癌（非小细胞肺癌的亚型）的非吸烟者和已戒烟的轻度吸烟者更有可能出现表皮生长因子突变，但突变会在所有类型的患者中发生。位于美国的生物技术公司健赞（此公司已于2011年由赛诺菲药业并购）已开发出检测表皮生长因子突变的方式。^[14]

胰脏癌

FDA于2005年11月核准厄洛替尼联合吉西他滨用于治疗局部晚期、不可切除或转移性胰脏癌。^[15]

抗药性

患者对厄洛替尼，与其他三磷酸腺苷（ATP）竞争性小分子酪胺酸激酶抑制剂（例如治疗慢性髓细胞性白血病的伊马替尼）一样，会迅速产生抗药性。在厄洛替尼，此情况通常发生在治疗开始后8-12个月。超过50%的抗药性是由表皮生长因子受体激酶结构域的三磷酸腺苷结合囊袋中的突变引起，涉及的是将一个小的极性苏氨酸残基替换为一个大的非极性甲硫氨酸残基（T790M）。^[16]

大约20%的抗药性是由肝细胞生长因子受体（英语：hepatocyte growth factor receptor）扩增所引起，这驱动ERBB3（英语：ERBB3）（ErbB蛋白家族中的一员）依赖性的磷酸肌醇3-激酶（一个参与诸如细胞生长、增殖、分化、移动、存活和胞内运输等细胞功能的酶家族，从而也参与癌症）活化，而促进癌细胞的生长和存活。^[17]^[18]

常见

大多数使用者均会出现皮疹。类似于痤疮，主要发生在脸部和颈部，在大多数情况下都会自行消失，即使继续使用也是如此。一些临床研究显示皮肤反应的严重程度与存活率增加之间存在相关性，但尚未进行定量评估。^[19]刊载于2004年《临床肿瘤学杂志（英语：Journal of Clinical Oncology）》的研究报告称"皮疹似乎是表彰有临床疗效的标志，但这一发现应透过目前和未来的研究中加以证实。"^[20] 癌症研究与临床肿瘤学杂志（英语：Journal of Cancer Research and Clinical Oncology）刊载的通讯《肺癌前沿（Lung Cancer Frontiers ）》在2003年10月报导，"有中度至重度皮肤反应（皮疹）的患者存活率较仅有轻度反应或无皮肤反应的患者高得多。"^[21]
腹泻
食欲不振
疲劳^[10]
局部脱发（部分，而非大片脱落。）

稀有

间质性肺炎，特征为咳嗽和呼吸困难逐渐加剧。如果患者的呼吸状况突然恶化，则应高度怀疑罹患间质性肺炎的可能。
毛发内生，例如睫毛
胃肠道毒性
- 严重或致命的肠胃穿孔
皮肤毒性
- 大疱、起泡和剥落性皮肤病（有些会致命）
- 史蒂芬斯-强森症候群/中毒性表皮坏死松解症（英语：toxic epidermal necrolysis）^[22]
眼部疾病
- 角膜病变
肺部毒性
- 间质性肺炎
- 隐源性组织化肺炎（英语：Cryptogenic organizing pneumonia） (COP)
- 肺纤维化
- 致命不对称间质性肺病^[23]

厄洛替尼不是肝脏有机阴离子转运蛋白家族（英语：Organo Anion Transporter Family）（OATP1B1或OATP1B3）的基质。此外，厄洛替尼不是OATP1B1或OATP1B3转运蛋白的抑制剂。^[24] Also, erlotinib is not an inhibitor of OATP-1B1 or OATP-1B3 transporter.^[25]

厄洛替尼主要经由肝脏酵素CYP3A4（细胞色素P450 3A4酶）代谢。诱导这种酵素（即刺激其产生）的化合物，例如贯叶连翘（欧美常用的草药），会降低厄洛替尼于使用者体内的浓度，而CYP3A4抑制剂会增加其浓度。^[26]

厄洛替尼是一种表皮生长因子受体抑制剂（EGFR抑制剂）。该药物继吉非替尼（商品名称Iressa）之后推出，吉非替尼是此类型药物中的第一种。厄洛替尼专门针对表皮生长因子受体 (EGFR) 酪胺酸激酶，此激酶在各种形式的癌症中高度表达，偶尔会发生突变。它以可逆的方式与受体的三磷酸腺苷 (ATP) 结合位点结合。^[27]为传递讯号，两个EGFR分子需要结合在一起形成蛋白二聚体。然后，它们利用ATP分子在酪胺酸残基上相互转磷酸化，产生磷酸酪胺酸残基，将磷酸酪胺酸结合蛋白募集到EGFR上，组装蛋白复合物，将讯号级联转导至细胞核或活化其他细胞生化过程。当厄洛替尼与EGFR结合时，EGFR中无法形成磷酸酪胺酸残基，且不会启动讯号级联。

此药物在美国由基因泰克^[3]和OSI制药（英语：OSI Pharmaceuticals）^[28]销售，在其他地方由罗氏药业销售。^[29]

药物的美国专利于2020年到期。^[30]迈兰药业曾针对OSI制药于厄洛替尼专利发动挑战，美国德拉瓦州联邦地区法院于2012年5月宣布判决，将迈兰药业的挑战驳回。^[31]

在印度，罗氏药业为厄洛替尼的专利权于2008年对生产通用名药物的印度西普拉有限公司发起诉讼（西普拉的产品价格仅为罗氏的三分之一^[32]），迄2017年，两造决定撤回侵权之诉，达成和解。^[33]^[34]

[1]
Erlotinib (Tarceva) Use During Pregnancy. Drugs.com. 2019-11-01 [2019-12-23]. （原始内容存档于12 November 2019）.
[2]
Tarceva (Erlotinib hydrochloride). Roche Products Pty Limited. Australian Product Information. 2022-08-31.
[3]
Tarceva- erlotinib hydrochloride tablet. DailyMed. 2018-12-12 [2019-12-23]. （原始内容存档于2020-08-06）.
[4]
Erlotinib Monograph for Professionals. Drugs.com. [2019-11-12]. （原始内容存档于2019-12-24）.
[5]
Drug Approval Package: Tarceva (Erlotinib) NDA #021743. U.S. Food and Drug Administration (FDA). 2005-03-28 [2019-12-23]. （原始内容存档于2019-12-23）.
[6]
Organization, World Health. World Health Organization model list of essential medicines: 21st list 2019. World Health Organization. 2019. hdl:10665/325771.
[7]
Generic Tarceva Availability. Drugs.com. 2024-09-11 [2024-09-24].
[8]
2009 - SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC.. [18 December 2010]. （原始内容存档于2010-12-22）.
[9]
April 2010 - Tarceva Indication Announcement Letter (PDF). [2010-12-18]. （原始内容存档 (PDF)于2011-07-16）.
[10]
Gijtenbeek RG, van der Noort V, Aerts JG, Staal-van den Brekel JA, Smit EF, Krouwels FH, Wilschut FA, Hiltermann TJ, Timens W, Schuuring E, Janssen JD, Goosens M, van den Berg PM, de Langen AJ, Stigt JA, van den Borne BE, Groen HJ, van Geffen WH, van der Wekken AJ. Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer. ERJ Open Research. October 2022, 8 (4): 00239–2022. PMC 9574558 . PMID 36267895. doi:10.1183/23120541.00239-2022.
[11]
Cohen MH, Johnson JR, Chen YF, Sridhara R, Pazdur R. FDA drug approval summary: erlotinib (Tarceva) tablets. The Oncologist. August 2005, 10 (7): 461–466. PMID 16079312. S2CID 10218263. doi:10.1634/theoncologist.10-7-461 .
[12]
Kobayashi K, Hagiwara K. Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC). Targeted Oncology. March 2013, 8 (1): 27–33. PMC 3591525 . PMID 23361373. doi:10.1007/s11523-013-0258-9.
[13]
Qi WX, Shen Z, Lin F, Sun YJ, Min DL, Tang LN, He AN, Yao Y. Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Asian Pacific Journal of Cancer Prevention. 2012, 13 (10): 5177–5182. PMID 23244131. doi:10.7314/APJCP.2012.13.10.5177 .
[14]
Roche obtains license for EGFR lung cancer assays and will develop Tarceva companion diagnostic test. Roche (新闻稿). [2020-01-10]. （原始内容存档于2022-02-24）.
[15]
Takimoto CH, Calvo E, Principles of Oncologic Pharmacotherapy, 2009-04-15 [2009-06-18], （原始内容存档于2009-05-15）
[16]
Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, Ladanyi M, Miller VA, Pao W. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clinical Cancer Research. November 2006, 12 (21): 6494–6501. PMID 17085664. doi:10.1158/1078-0432.CCR-06-1570 .
[17]
Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Jänne PA. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. May 2007, 316 (5827): 1039–1043. Bibcode:2007Sci...316.1039E. PMID 17463250. S2CID 23254145. doi:10.1126/science.1141478 .
[18]
Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proceedings of the National Academy of Sciences of the United States of America. December 2007, 104 (52): 20932–20937. Bibcode:2007PNAS..10420932B. PMC 2409244 . PMID 18093943. doi:10.1073/pnas.0710370104 .
[19]
Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M. Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. January 2006, 51 (1): 89–96. PMID 16290256. doi:10.1016/j.lungcan.2005.09.002.
[20]
Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, Rigas J, Clark GM, Santabárbara P, Bonomi P. Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. Journal of Clinical Oncology. August 2004, 22 (16): 3238–3247. PMID 15310767. doi:10.1200/JCO.2004.11.057 .
[21]
Petty TL. Determinants of Tumor Response and Survival With Erlotinib in Patients With Non—Small-Cell Lung Cancer. Journal of Clinical Oncology. 2003, 1 (17): 3–4.
[22]
Li X, Kamenecka TM, Cameron MD. Cytochrome P450-mediated bioactivation of the epidermal growth factor receptor inhibitor erlotinib to a reactive electrophile. Drug Metabolism and Disposition. July 2010, 38 (7): 1238–1245. PMC 3202369 . PMID 20382753. doi:10.1124/dmd.109.030361.
[23]
Ren S, Li Y, Li W, Zhao Z, Jin C, Zhang D. Fatal asymmetric interstitial lung disease after erlotinib for lung cancer. Respiration; International Review of Thoracic Diseases. 2012, 84 (5): 431–435. PMID 22889962. doi:10.1159/000339508 .
[24]
Khurana V, Minocha M, Pal D, Mitra AK. Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug Metabolism and Drug Interactions. March 2014, 29 (3): 179–190. PMC 4407685 . PMID 24643910. doi:10.1515/dmdi-2013-0062.
[25]
Khurana V, Minocha M, Pal D, Mitra AK. Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors. Drug Metabolism and Drug Interactions. May 2014, 29 (4): 249–259. PMC 4407688 . PMID 24807167. doi:10.1515/dmdi-2014-0014.
[26]
Haberfeld, H (编). Austria-Codex 2010/2011. Vienna: Österreichischer Apothekerverlag. 2010 （德语）.
[27]
Raymond E, Faivre S, Armand JP. Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000, 60 (Suppl 1): 15–23; discussion 41–2. PMID 11129168. S2CID 10555942. doi:10.2165/00003495-200060001-00002 .
[28]
Adis International Ltd. Erlotinib: CP 358774, NSC 718781, OSI 774, R 1415. Drugs in R&D. 2003, 4 (4): 243–248. PMID 12848590. doi:10.2165/00126839-200304040-00006.
[29]
FDA Approves Roche Test as CDx for Tarceva for Treating Certain NSCLC Patients. GenomeWeb. 2013-05-15 [2020-01-10]. （原始内容存档于2019-09-06）（美国英语）.
[30]
Erlotinib - Generic Drug Details. DrugPatentWatch.com. （原始内容存档于2016-04-28）.
[31]
OSI Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc.. casetext. 2012-05-01 [2024-09-24].
[32]
Roche Vs Cipla: Final leg of battle over Tarceva Patent. RNA Technology and IP Attorneys. 2016-02-02 [2024-09-24].
[33]
The end of Roche vs. Cipla infringement lawsuit. invntree. [2024-09-24].
[34]
Roche v. Cipla- The Sense of An Ending. SpicyIP. [2024-09-24].

Erlotinib. National Cancer Institute.

[Drugs.com_pregnancy-1] [1]
Erlotinib (Tarceva) Use During Pregnancy. Drugs.com. 2019-11-01 [2019-12-23]. （原始内容存档于12 November 2019）.

[Tarceva_PI-2] [2]
Tarceva (Erlotinib hydrochloride). Roche Products Pty Limited. Australian Product Information. 2022-08-31.

[Tarceva_label-3] [3]
Tarceva- erlotinib hydrochloride tablet. DailyMed. 2018-12-12 [2019-12-23]. （原始内容存档于2020-08-06）.

[AHFS2019-4] [4]
Erlotinib Monograph for Professionals. Drugs.com. [2019-11-12]. （原始内容存档于2019-12-24）.

[5] [5]
Drug Approval Package: Tarceva (Erlotinib) NDA #021743. U.S. Food and Drug Administration (FDA). 2005-03-28 [2019-12-23]. （原始内容存档于2019-12-23）.

[WHO21st-6] [6]
Organization, World Health. World Health Organization model list of essential medicines: 21st list 2019. World Health Organization. 2019. hdl:10665/325771.

[7] [7]
Generic Tarceva Availability. Drugs.com. 2024-09-11 [2024-09-24].

[8] [8]
2009 - SATURN: A double-blind, randomized, phase III study of maintenance erlotinib versus placebo following nonprogression with first-line platinum-based chemotherapy in patients with advanced NSCLC.. [18 December 2010]. （原始内容存档于2010-12-22）.

[9] [9]
April 2010 - Tarceva Indication Announcement Letter (PDF). [2010-12-18]. （原始内容存档 (PDF)于2011-07-16）.

[Gijtenbeek_00239–2022-10] [10]
Gijtenbeek RG, van der Noort V, Aerts JG, Staal-van den Brekel JA, Smit EF, Krouwels FH, Wilschut FA, Hiltermann TJ, Timens W, Schuuring E, Janssen JD, Goosens M, van den Berg PM, de Langen AJ, Stigt JA, van den Borne BE, Groen HJ, van Geffen WH, van der Wekken AJ. Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer. ERJ Open Research. October 2022, 8 (4): 00239–2022. PMC 9574558 . PMID 36267895. doi:10.1183/23120541.00239-2022.

[11] [11]
Cohen MH, Johnson JR, Chen YF, Sridhara R, Pazdur R. FDA drug approval summary: erlotinib (Tarceva) tablets. The Oncologist. August 2005, 10 (7): 461–466. PMID 16079312. S2CID 10218263. doi:10.1634/theoncologist.10-7-461 .

[12] [12]
Kobayashi K, Hagiwara K. Epidermal growth factor receptor (EGFR) mutation and personalized therapy in advanced nonsmall cell lung cancer (NSCLC). Targeted Oncology. March 2013, 8 (1): 27–33. PMC 3591525 . PMID 23361373. doi:10.1007/s11523-013-0258-9.

[Qi-13] [13]
Qi WX, Shen Z, Lin F, Sun YJ, Min DL, Tang LN, He AN, Yao Y. Comparison of the efficacy and safety of EFGR tyrosine kinase inhibitor monotherapy with standard second-line chemotherapy in previously treated advanced non-small-cell lung cancer: a systematic review and meta-analysis. Asian Pacific Journal of Cancer Prevention. 2012, 13 (10): 5177–5182. PMID 23244131. doi:10.7314/APJCP.2012.13.10.5177 .

[14] [14]
Roche obtains license for EGFR lung cancer assays and will develop Tarceva companion diagnostic test. Roche (新闻稿). [2020-01-10]. （原始内容存档于2022-02-24）.

[15] [15]
Takimoto CH, Calvo E, Principles of Oncologic Pharmacotherapy, 2009-04-15 [2009-06-18], （原始内容存档于2009-05-15）

[pmid17085664-16] [16]
Balak MN, Gong Y, Riely GJ, Somwar R, Li AR, Zakowski MF, Chiang A, Yang G, Ouerfelli O, Kris MG, Ladanyi M, Miller VA, Pao W. Novel D761Y and common secondary T790M mutations in epidermal growth factor receptor-mutant lung adenocarcinomas with acquired resistance to kinase inhibitors. Clinical Cancer Research. November 2006, 12 (21): 6494–6501. PMID 17085664. doi:10.1158/1078-0432.CCR-06-1570 .

[pmid17463250-17] [17]
Engelman JA, Zejnullahu K, Mitsudomi T, Song Y, Hyland C, Park JO, Lindeman N, Gale CM, Zhao X, Christensen J, Kosaka T, Holmes AJ, Rogers AM, Cappuzzo F, Mok T, Lee C, Johnson BE, Cantley LC, Jänne PA. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science. May 2007, 316 (5827): 1039–1043. Bibcode:2007Sci...316.1039E. PMID 17463250. S2CID 23254145. doi:10.1126/science.1141478 .

[pmid18093943-18] [18]
Bean J, Brennan C, Shih JY, Riely G, Viale A, Wang L, Chitale D, Motoi N, Szoke J, Broderick S, Balak M, Chang WC, Yu CJ, Gazdar A, Pass H, Rusch V, Gerald W, Huang SF, Yang PC, Miller V, Ladanyi M, Yang CH, Pao W. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proceedings of the National Academy of Sciences of the United States of America. December 2007, 104 (52): 20932–20937. Bibcode:2007PNAS..10420932B. PMC 2409244 . PMID 18093943. doi:10.1073/pnas.0710370104 .

[19] [19]
Dudek AZ, Kmak KL, Koopmeiners J, Keshtgarpour M. Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. January 2006, 51 (1): 89–96. PMID 16290256. doi:10.1016/j.lungcan.2005.09.002.

[20] [20]
Pérez-Soler R, Chachoua A, Hammond LA, Rowinsky EK, Huberman M, Karp D, Rigas J, Clark GM, Santabárbara P, Bonomi P. Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer. Journal of Clinical Oncology. August 2004, 22 (16): 3238–3247. PMID 15310767. doi:10.1200/JCO.2004.11.057 .

[21] [21]
Petty TL. Determinants of Tumor Response and Survival With Erlotinib in Patients With Non—Small-Cell Lung Cancer. Journal of Clinical Oncology. 2003, 1 (17): 3–4.

[22] [22]
Li X, Kamenecka TM, Cameron MD. Cytochrome P450-mediated bioactivation of the epidermal growth factor receptor inhibitor erlotinib to a reactive electrophile. Drug Metabolism and Disposition. July 2010, 38 (7): 1238–1245. PMC 3202369 . PMID 20382753. doi:10.1124/dmd.109.030361.

[23] [23]
Ren S, Li Y, Li W, Zhao Z, Jin C, Zhang D. Fatal asymmetric interstitial lung disease after erlotinib for lung cancer. Respiration; International Review of Thoracic Diseases. 2012, 84 (5): 431–435. PMID 22889962. doi:10.1159/000339508 .

[pmid24643910-24] [24]
Khurana V, Minocha M, Pal D, Mitra AK. Role of OATP-1B1 and/or OATP-1B3 in hepatic disposition of tyrosine kinase inhibitors. Drug Metabolism and Drug Interactions. March 2014, 29 (3): 179–190. PMC 4407685 . PMID 24643910. doi:10.1515/dmdi-2013-0062.

[Khurana_V_2014-25] [25]
Khurana V, Minocha M, Pal D, Mitra AK. Inhibition of OATP-1B1 and OATP-1B3 by tyrosine kinase inhibitors. Drug Metabolism and Drug Interactions. May 2014, 29 (4): 249–259. PMC 4407688 . PMID 24807167. doi:10.1515/dmdi-2014-0014.

[26] [26]
Haberfeld, H (编). Austria-Codex 2010/2011. Vienna: Österreichischer Apothekerverlag. 2010 （德语）.

[27] [27]
Raymond E, Faivre S, Armand JP. Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000, 60 (Suppl 1): 15–23; discussion 41–2. PMID 11129168. S2CID 10555942. doi:10.2165/00003495-200060001-00002 .

[28] [28]
Adis International Ltd. Erlotinib: CP 358774, NSC 718781, OSI 774, R 1415. Drugs in R&D. 2003, 4 (4): 243–248. PMID 12848590. doi:10.2165/00126839-200304040-00006.

[29] [29]
FDA Approves Roche Test as CDx for Tarceva for Treating Certain NSCLC Patients. GenomeWeb. 2013-05-15 [2020-01-10]. （原始内容存档于2019-09-06）（美国英语）.

[30] [30]
Erlotinib - Generic Drug Details. DrugPatentWatch.com. （原始内容存档于2016-04-28）.

[31] [31]
OSI Pharmaceuticals, Inc. v. Mylan Pharmaceuticals Inc.. casetext. 2012-05-01 [2024-09-24].

[32] [32]
Roche Vs Cipla: Final leg of battle over Tarceva Patent. RNA Technology and IP Attorneys. 2016-02-02 [2024-09-24].

[33] [33]
The end of Roche vs. Cipla infringement lawsuit. invntree. [2024-09-24].

[34] [34]
Roche v. Cipla- The Sense of An Ending. SpicyIP. [2024-09-24].

[4]

[1]

[2]

[3]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

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