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厄洛替尼所致皮肤白细胞破碎性血管炎:仅仅是一种不良事件还是药物疗效的潜在标志物?

Cutaneous leukocytoclastic vasculitis due to erlotinib: just an adverse event or also a putative marker of drug efficacy?

作者信息

Brandi Giovanni, Venturi Michela, Dika Emi, Maibach Howard, Patrizi Annalisa, Biasco Guido

机构信息

Department of Specialised, Experimental and Diagnostic Medicine, "L. and A. Seràgnoli" Hematology and Oncological Sciences Institute.

出版信息

Cutan Ocul Toxicol. 2013 Oct;32(4):336-8. doi: 10.3109/15569527.2013.780179. Epub 2013 Mar 27.

DOI:10.3109/15569527.2013.780179
PMID:23534992
Abstract

Erlotinib is a targeted anticancer therapy with selective inhibitory activity for tyrosine kinase of the epidermal growth factor receptor (EGFR). Different skin reactions have been described linked to these drugs. There are no other reports about erlotinib-induced leukocytoclastic vasculitis (LV) in the erlotinib-bevacizumab regimen for bone metastasis, from a relapsed hepatocellular carcinoma (HCC) in liver-transplanted patients. In our patient a dose reduction and then the suspension of erlotinib was required. After a 2 week withdrawal, the drug was re-challenged at a lower dose. The patient continued it without any skin recurrence, and resulted progression free for 16 months. Thus, we underline the possibility to avoid a permanent withdrawal of erlotinib and to rechallenge with it without any cutaneous toxicity, particularly in patients benefiting from this drug. Moreover, the median overall survival from the initial treatment of bone relapsed patients after liver transplant for HCC is found to be less than 5 months, while our patient died 5 years later. This longer survival encourages further investigations to assess also whether LV, even if rare, might be used as a marker of antitumor efficacy of EGFR inhibitors.

摘要

厄洛替尼是一种针对表皮生长因子受体(EGFR)酪氨酸激酶具有选择性抑制活性的靶向抗癌疗法。已经描述了与这些药物相关的不同皮肤反应。在肝移植患者复发性肝细胞癌(HCC)骨转移的厄洛替尼 - 贝伐单抗方案中,尚无关于厄洛替尼诱导白细胞破碎性血管炎(LV)的其他报道。在我们的患者中,需要降低厄洛替尼剂量,然后暂停用药。停药2周后,以较低剂量重新使用该药物。患者继续使用该药物,未出现任何皮肤复发情况,并且无进展生存16个月。因此,我们强调有可能避免永久停用厄洛替尼,并在无任何皮肤毒性的情况下重新使用该药物,特别是在受益于这种药物的患者中。此外,肝移植治疗HCC后骨转移患者初始治疗后的中位总生存期不到5个月,而我们的患者5年后死亡。这种较长的生存期鼓励进一步研究,以评估LV即使罕见,是否也可作为EGFR抑制剂抗肿瘤疗效的标志物。

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1
Cutaneous leukocytoclastic vasculitis due to erlotinib: just an adverse event or also a putative marker of drug efficacy?厄洛替尼所致皮肤白细胞破碎性血管炎:仅仅是一种不良事件还是药物疗效的潜在标志物?
Cutan Ocul Toxicol. 2013 Oct;32(4):336-8. doi: 10.3109/15569527.2013.780179. Epub 2013 Mar 27.
2
Leukocytoclastic vasculitis during treatment with the oral EGFR tyrosine kinase inhibitor erlotinib.口服表皮生长因子受体酪氨酸激酶抑制剂厄洛替尼治疗期间的白细胞破碎性血管炎。
Ann Oncol. 2007 Sep;18(9):1582-3. doi: 10.1093/annonc/mdm420.
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Phase II study of Erlotinib (OSI-774) in patients with advanced hepatocellular cancer.厄洛替尼(OSI-774)用于晚期肝细胞癌患者的II期研究。
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Phase 2 study of erlotinib in patients with unresectable hepatocellular carcinoma.厄洛替尼用于不可切除肝细胞癌患者的2期研究。
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[A case of cutaneous vasculitis caused by erlotinib treatment and a review of literature].[一例由厄洛替尼治疗引起的皮肤血管炎病例及文献复习]
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Successful erlotinib rechallenge for leptomeningeal metastases of lung adenocarcinoma after erlotinib-induced interstitial lung disease: a case report and review of the literature.厄洛替尼诱导的间质性肺病后肺腺癌脑膜转移再次成功厄洛替尼治疗:病例报告及文献复习。
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A phase II trial of erlotinib in patients with EGFR wild-type advanced non-small-cell lung cancer.表皮生长因子受体野生型晚期非小细胞肺癌患者厄洛替尼的 II 期临床试验。
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Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study.瑞戈非尼作为中晚期肝细胞癌二线治疗药物的多中心、开放标签、Ⅱ期安全性研究。
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Annular leukocytoclastic vasculitis associated with sorafenib administration.与索拉非尼给药相关的环状白细胞破碎性血管炎。
J Drugs Dermatol. 2010 Jun;9(6):697-8.

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Front Oncol. 2025 Jan 23;15:1523541. doi: 10.3389/fonc.2025.1523541. eCollection 2025.
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Disseminate Cutaneous Vasculitis Associated with Durvalumab Treatment-Case Report, Mini-Review on Cutaneous Side Effects of Immune Checkpoint Inhibitor Therapies with Machine Learning Perspectives.度伐利尤单抗治疗相关的播散性皮肤血管炎——病例报告,基于机器学习视角对免疫检查点抑制剂疗法皮肤副作用的小型综述
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EGFR Inhibitors-related Panniculitis: A New Side Effect.
表皮生长因子受体抑制剂相关脂膜炎:一种新的副作用。
Indian Dermatol Online J. 2019 May-Jun;10(3):319-321. doi: 10.4103/idoj.IDOJ_273_18.
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Cutaneous leukocytoclastic vasculitis associated with erlotinib treatment: A case report and review of the literature.与厄洛替尼治疗相关的皮肤白细胞破碎性血管炎:一例报告并文献复习
Exp Ther Med. 2019 Feb;17(2):1128-1131. doi: 10.3892/etm.2018.6988. Epub 2018 Nov 19.
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Successful rechallenge with ceritinib after leukocytoclastic vasculitis during ceritinib treatment for non-small cell lung cancer harboring the EML4-ALK fusion protein.在携带EML4-ALK融合蛋白的非小细胞肺癌患者使用色瑞替尼治疗期间发生白细胞破碎性血管炎后成功再次使用色瑞替尼。
Oncotarget. 2018 Apr 13;9(28):20213-20218. doi: 10.18632/oncotarget.24765.
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Cutaneous Leukocytoclastic Vasculitis Associated with Erlotinib.与厄洛替尼相关的皮肤白细胞破碎性血管炎
Indian J Dermatol. 2016 Mar-Apr;61(2):238. doi: 10.4103/0019-5154.177793.
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A spectrum of cutaneous toxicities from erlotinib may be a robust clinical marker for non-small-cell lung therapy: a case report and literature review.厄洛替尼引起的一系列皮肤毒性可能是非小细胞肺癌治疗的一个有力临床标志物:一例病例报告及文献综述
Onco Targets Ther. 2015 Apr 23;8:943-6. doi: 10.2147/OTT.S83888. eCollection 2015.