Department of Thoracic Oncology, 1st Affiliated Hospital, Zhejiang University School of Medicine, 79 Qing Chun Road, Hangzhou 310003, China.
Jpn J Clin Oncol. 2013 Feb;43(2):200-4. doi: 10.1093/jjco/hys209. Epub 2012 Dec 21.
Icotinib hydrochloride, a novel inhibitor of epidermal growth factor receptor tyrosine kinase, has been approved by the State Food and Drug Administration for the treatment of advanced non-small-cell lung cancer. Up to date, cutaneous response to icotinib is largely unknown. Here we report an uncommon lesional phenomenon in a 56-year-old Chinese male with non-small-cell lung cancer, who received icotinib as a second-line treatment. Characteristic papulopustular rash on the chest and back was observed 4 days later. Interestingly, the rash completely spares a pre-irradiated area. The immunohistochemical study in the lesional skin area and spared skin area revealed a significant decrease in CD1a(+) Langerhans cells, Ki-67 as well as FGFR2 in the spared area than in the lesional area. Thus, the present case indicated that loss of the basal layer of proliferative cells and antigen-presenting cells (Langerhans cell), as well as the down-regulation of FGFR2 signaling in the pre-irradiated skin area, may join forces in inhibiting icotinib-associated cutaneous reactions. To our knowledge, this is the first report of both lesional area and lesion-spared area in a Chinese male receiving treatment with a new epidermal growth factor receptor-tyrosine kinase inhibitor (icotinib). The immunohistochemical reactions described here also provide new insight into the pathogenesis of epidermal growth factor receptor-tyrosine kinase inhibitor-related skin toxicities, and the role that other tyrosine kinase receptors (including FGFR) played in non-small-cell lung cancer.
盐酸埃克替尼,一种新型的表皮生长因子受体酪氨酸激酶抑制剂,已被国家食品药品监督管理局批准用于治疗晚期非小细胞肺癌。迄今为止,对埃克替尼的皮肤反应还知之甚少。在这里,我们报告了一例 56 岁中国男性非小细胞肺癌患者在接受埃克替尼二线治疗后出现的一种不常见的皮损现象。患者胸部和背部出现特征性的丘疹脓疱疹,在接受埃克替尼治疗 4 天后观察到。有趣的是,皮疹完全避开了预先照射的区域。对皮损区和未皮损区的皮肤进行免疫组化研究显示,未皮损区的 CD1a(+)朗格汉斯细胞、Ki-67 和 FGFR2 显著减少。因此,本病例表明,增殖细胞和抗原呈递细胞(朗格汉斯细胞)的基底层丧失,以及预先照射皮肤区域中 FGFR2 信号的下调,可能共同抑制埃克替尼相关的皮肤反应。据我们所知,这是首例接受新型表皮生长因子受体酪氨酸激酶抑制剂(埃克替尼)治疗的中国男性患者的皮损区和未皮损区报告。这里描述的免疫组化反应也为表皮生长因子受体酪氨酸激酶抑制剂相关皮肤毒性的发病机制提供了新的见解,以及其他酪氨酸激酶受体(包括 FGFR)在非小细胞肺癌中的作用。