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管理表皮生长因子受体抑制剂的皮肤毒性

Managing dermatologic toxicities of epidermal growth factor receptor inhibitors.

作者信息

Chou Lillian S, Garey Jody, Oishi Karen, Kim Edward

机构信息

University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

出版信息

Clin Lung Cancer. 2006 Dec;8 Suppl 1:S15-22. doi: 10.3816/clc.2006.s.009.

DOI:10.3816/clc.2006.s.009
PMID:17239286
Abstract

There is considerable evidence that epidermal growth factor receptor (EGFR) plays an important role in non-small-cell lung cancer tumor growth and proliferation. Clinical experience with EGFR inhibitors, such as erlotinib, gefitinib, and cetuximab, has suggested that there are subgroups of patients with non-small-cell lung cancer that demonstrate dramatic responses to these agents. Researchers have sought to determine whether molecular or clinical characteristics correlate with therapeutic outcomes. Rash, the most commonly reported adverse effect of anti-EGFR therapy, has also been examined as a potential marker of response. Several trials evaluating anti-EGFR therapies have reported a positive correlation between rash and response and even rash and survival. If rash is truly a predictor of outcome, it becomes imperative that clinicians identify effective methods for managing this toxicity to avoid unwanted dose reduction, therapy interruption, delay, or discontinuation in patients experiencing a therapeutic benefit. Unfortunately, because of a lack of well-defined rash etiology, variability of use, and interpretation of rash grading scales, as well as a lack of clinical trials evaluating approaches to rash management, we are left without systematic, evidence-based guidelines for treatment. Preliminary results of a prospective study evaluating a rash treatment algorithm developed at the University of Texas M. D. Anderson Cancer Center have been positive, and there is universal agreement that initiation of more prospective trials to evaluate EGFR-inhibitor rash management is needed.

摘要

有大量证据表明,表皮生长因子受体(EGFR)在非小细胞肺癌的肿瘤生长和增殖中起重要作用。使用厄洛替尼、吉非替尼和西妥昔单抗等EGFR抑制剂的临床经验表明,非小细胞肺癌患者中存在一些亚组,这些亚组对这些药物表现出显著反应。研究人员试图确定分子特征或临床特征是否与治疗结果相关。皮疹是抗EGFR治疗最常报告的不良反应,也被作为一种潜在的反应标志物进行了研究。几项评估抗EGFR治疗的试验报告了皮疹与反应之间、甚至皮疹与生存之间的正相关。如果皮疹真的是结果的预测指标,那么临床医生必须确定有效的方法来管理这种毒性,以避免在有治疗益处的患者中出现不必要的剂量减少、治疗中断、延迟或停药。不幸的是,由于缺乏明确的皮疹病因、使用的变异性、皮疹分级量表的解释,以及缺乏评估皮疹管理方法的临床试验,我们没有系统的、基于证据的治疗指南。德克萨斯大学MD安德森癌症中心开发的一项评估皮疹治疗算法的前瞻性研究的初步结果是积极的,并且人们普遍认为需要开展更多前瞻性试验来评估EGFR抑制剂相关皮疹的管理。

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Managing dermatologic toxicities of epidermal growth factor receptor inhibitors.管理表皮生长因子受体抑制剂的皮肤毒性
Clin Lung Cancer. 2006 Dec;8 Suppl 1:S15-22. doi: 10.3816/clc.2006.s.009.
2
Rash as a surrogate marker for efficacy of epidermal growth factor receptor inhibitors in lung cancer.皮疹作为肺癌中表皮生长因子受体抑制剂疗效的替代标志物。
Clin Lung Cancer. 2006 Dec;8 Suppl 1:S7-14. doi: 10.3816/clc.2006.s.008.
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A decrease in D-dimer concentration and an occurrence of skin rash as iatrogenic events and complementary predictors of survival in lung cancer patients treated with EGFR tyrosine kinase inhibitors.D-二聚体浓度降低和皮疹出现作为接受EGFR酪氨酸激酶抑制剂治疗的肺癌患者的医源性事件及生存的补充预测指标。
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Clinical significance and treatment of skin rash from erlotinib in non-small cell lung cancer patients: results of an Experts Panel Meeting.厄洛替尼所致非小细胞肺癌患者皮疹的临床意义及治疗:专家小组会议结果
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Skin toxicities associated with epidermal growth factor receptor inhibitors.与表皮生长因子受体抑制剂相关的皮肤毒性。
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Dosing to rash?--The role of erlotinib metabolic ratio from patient serum in the search of predictive biomarkers for EGFR inhibitor-mediated skin rash.皮疹的给药剂量?——患者血清中厄洛替尼代谢率在寻找表皮生长因子受体(EGFR)抑制剂介导皮疹的预测生物标志物中的作用。
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Clinical impact of switching to a second EGFR-TKI after a severe AE related to a first EGFR-TKI in EGFR-mutated NSCLC.表皮生长因子受体突变型非小细胞肺癌患者使用第一代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)发生严重不良反应后切换使用第二代 EGFR-TKI 的临床影响。
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Inhibition of the epidermal growth factor receptor in combined modality treatment for locally advanced non-small cell lung cancer.表皮生长因子受体抑制在局部晚期非小细胞肺癌综合治疗中的应用
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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.在接受吉非替尼治疗既往治疗过的晚期或转移性非小细胞肺癌患者中,皮疹和支气管肺泡组织学与临床获益相关。
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Erlotinib-induced skin rash in patients with non-small-cell lung cancer: pathogenesis, clinical significance, and management.厄洛替尼诱发非小细胞肺癌患者皮疹:发病机制、临床意义及处理
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引用本文的文献

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How well does the MESTT correlate with CTCAE scale for the grading of dermatological toxicities associated with oral tyrosine kinase inhibitors?MESTT 与 CTCAE 量表在评估与口服酪氨酸激酶抑制剂相关的皮肤毒性方面的相关性如何?
Support Care Cancer. 2011 Oct;19(10):1667-74. doi: 10.1007/s00520-010-0999-2. Epub 2010 Sep 5.
2
Metabolism considerations for kinase inhibitors in cancer treatment.癌症治疗中激酶抑制剂的代谢考虑因素。
Expert Opin Drug Metab Toxicol. 2010 Oct;6(10):1175-93. doi: 10.1517/17425255.2010.506873.
3
Rational use of cetuximab in the treatment of advanced non-small cell lung cancer.
西妥昔单抗治疗晚期非小细胞肺癌的合理应用。
Onco Targets Ther. 2009 Feb 18;2:251-60. doi: 10.2147/ott.s4761.
4
Cytochrome P450-mediated bioactivation of the epidermal growth factor receptor inhibitor erlotinib to a reactive electrophile.细胞色素 P450 介导的表皮生长因子受体抑制剂厄洛替尼的生物活化,生成一个反应性亲电试剂。
Drug Metab Dispos. 2010 Jul;38(7):1238-45. doi: 10.1124/dmd.109.030361. Epub 2010 Apr 9.