Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225
Cutaneous side-effects in cancer patients treated with the antiepidermal growth factor receptor antibody C225
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DOI：
10.1046/j.1365-2133.2001.04226.x
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发表时间：
2001-01-01
影响因子：
10.3
通讯作者：
Halpern, AC
中科院分区：
文献类型：
--
作者：
Busam, KJ;Capodieci, P;Halpern, AC
研究背景C225是一种抗表皮生长因子受体（EGFR）的抗体，可抑制多种肿瘤细胞的生长。该抗体目前被用作癌症患者的几项临床试验中的治疗剂。目的确定和调查C225治疗癌症患者的皮肤副作用。方法我们临床检查了10例用C225治疗的患者，结果C225治疗后最常见的皮肤反应是皮肤上皮细胞增生，痤疮样毛囊疹，这是最明显的面部，胸部和上背部，通常表现为一个星期后开始治疗。C225单药治疗后，10例不同患者的形态学和临床发现时间的一致性强烈表明了抗体的直接生物学效应。其他皮肤病学副作用包括脚趾和手指的局部压痛性甲沟炎和口腔粘膜的小阿弗他溃疡。治疗前后（第8天）胸部皮肤的连续穿刺活检显示了两种主要反应模式：角化过度和扩张性毛囊漏斗周围的浅表真皮炎性细胞浸润和化脓性浅表毛囊炎。在两个活组织检查发现局灶性表皮内棘层松解。微生物培养未能揭示感染性病因。免疫组化和原位杂交结果显示，经C225处理后，表皮角质形成细胞中p27（Kip 1）的表达增加。结论p27（Kip 1）参与了EGFR对毛囊和表皮稳态的调节。
Background C225 is an antibody to the epidermal growth factor receptor (EGFR), and inhibits growth of various tumour cells. The antibody is currently being used as a therapeutic agent in several clinical trials of patients with carcinomas.Objectives To determine and investigate the cutaneous side-effects in cancer patients treated with C225.Methods We clinically examined 10 patients treated with C225, and performed immunohistochemical and in situ hybridization studies on skin biopsies.Results The most common cutaneous reaction to C225 therapy was the development of an acneiform follicular eruption, which was most pronounced on the face, chest and upper back and typically manifested a week after the onset of treatment. The consistency of the morphology and timing of the clinical findings in 10 different patients following monotherapy with C225 strongly suggested a direct biological effect of the antibody. Additional dermatological side-effects included focal areas of tender paronychial inflammation of toes and fingers and small aphthous ulcers of the oral mucosa. Serial punch biopsies of chest skin before and after treatment (at 8 days) revealed two main reaction patterns: a superficial dermal inflammatory cell infiltrate surrounding hyperkeratotic and ectatic follicular infundibula, and a suppurative superficial folliculitis. In two biopsies focal intraepidermal acantholysis was found. Microbiological cultures failed to reveal an infectious aetiology. Immunohistochemical and in situ hybridization studies on a subset of the biopsies showed an increase in the expression of p27(Kip1) in epidermal keratinocytes after treatment with C225.Conclusions Our findings support the concept that p27(Kip1) plays a part in the in vivo regulation of follicular and epidermal homeostasis by EGFR.