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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。

Successful rechallenge with ceritinib after leukocytoclastic vasculitis during ceritinib treatment for non-small cell lung cancer harboring the EML4-ALK fusion protein.

作者信息

Okimoto Tamio, Tsubata Yukari, Hotta Takamasa, Hamaguchi Megumi, Okuno Takae, Shiratsuki Yohei, Kodama Akari, Nakao Mika, Amano Yoshihiro, Hamaguchi Shunichi, Kurimoto Noriaki, Tobita Reiko, Isobe Takeshi

机构信息

Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine, Shimane, Japan.

Department of Dermatology, Shimane University Faculty of Medicine, Shimane, Japan.

出版信息

Oncotarget. 2018 Apr 13;9(28):20213-20218. doi: 10.18632/oncotarget.24765.

Abstract

Anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) dramatically improve progression-free survival compared to cytotoxic agents. It is therefore important to manage patients with ALK-TKIs until drug resistance occurs. Leukocytoclastic vasculitis (LCV) is a rare complication during cancer treatment and is associated with a variety of factors. Currently, it is unclear whether we should withdraw a treatment when drug-induced LCV develops. We report a 40-year-old man with advanced pulmonary adenocarcinoma harboring the EML4-ALK fusion protein who developed LCV during ceritinib treatment. Four weeks after withdrawing ceritinib, we could successfully perform rechallenge with ceritinib at the normal dose. Rapid and massive tumor apoptosis due to ceritinib treatment may lead to neoantigen release and immune complexes deposition. To the best of our knowledge, we report the first case of LCV in a patient during ALK-TKI treatment. Following this occurrence, we were able to successfully perform rechallenge with ceritinib. Therefore, key drugs used in a patient's treatment regimen should not be discontinued without careful evaluation, and we should also consider the possibility of rechallenge.

摘要

与细胞毒性药物相比,间变性淋巴瘤激酶(ALK)-酪氨酸激酶抑制剂(TKIs)显著提高了无进展生存期。因此,在出现耐药之前对使用ALK-TKIs的患者进行管理非常重要。白细胞破碎性血管炎(LCV)是癌症治疗期间的一种罕见并发症,与多种因素有关。目前,尚不清楚当发生药物性LCV时是否应停止治疗。我们报告了一名40岁患有晚期肺腺癌且携带EML4-ALK融合蛋白的男性,他在色瑞替尼治疗期间发生了LCV。停用色瑞替尼四周后,我们能够成功以正常剂量重新使用色瑞替尼进行挑战。色瑞替尼治疗导致的快速大量肿瘤凋亡可能导致新抗原释放和免疫复合物沉积。据我们所知,我们报告了ALK-TKI治疗期间患者发生LCV的首例病例。在此事件发生后,我们能够成功地重新使用色瑞替尼进行挑战。因此,在未进行仔细评估的情况下,不应停用患者治疗方案中使用的关键药物,我们还应考虑重新挑战的可能性。

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