表皮生长因子受体抑制剂诱发的皮肤黏膜反应4例临床分析及文献回顾

Clinical Analysis and Literature Review of Skin and Mucosal Reactions Induced by Epidermal Growth Factor Receptor Inhibitors

目的探讨肿瘤靶向治疗药物表皮生长因子受体抑制剂(EGFRIs)诱发皮肤黏膜反应的临床表现,分析不良反应的类型、严重程度及治疗效果,并进行文献回顾。方法对4例经EGFRIs治疗后发生皮肤黏膜不良反应的患者及既往国内外文献报道的156例亚洲患者进行临床分析,用美国国家癌症研究所不良反应评定标准4.0版标准评估严重程度及不良反应类型,总结EGFRIs相关皮肤黏膜反应的临床特点及治疗方法。结果共160例,其中男92例,女68例,年龄36~78岁。非小细胞肺癌(56.3%)是患者中最常见的癌症。多数患者在使用EGFRIs靶向治疗1~3周后出现皮肤黏膜反应。痤疮样皮疹124例(77.5%),皮肤干燥85例(53.1%),红斑脱屑38例(23.8%),甲沟炎及甲周化脓性肉芽肿34例(21.3%),毛发改变27例(16.9%),口腔黏膜炎13例(8.1%)。皮疹严重程度分级1~2级106例,≥3级54例。经对症处理2~4周后,大部分患者的不良反应得以控制,6例患者通过减少EGFRIs药物剂量以及9例患者中断治疗后不良反应得到控制。结论EGFRIs诱发的皮肤黏膜不良反应中,最常见的是痤疮样皮疹及皮肤干燥,皮肤黏膜反应严重程度以轻中度为主,经对症处理、减量或停药后症状可缓解。

Objective In order to explore the clinical features of skin and mucosal reactions induced by epidermal growth factor receptor inhibitors(EGFRIs).The type and severity of adverse reactions and the therapeutic effects are analyzed,and the literatures are reviewed.Methods A clinical analysis of four cases treated by EGFRIs and 156 Asian cases coming from literatures had been made.The type and severity of adverse reactions were evaluated by National Cancer Institute-Common Terminology Criteria for Adverse Events 4.0 standard(NCI-CTCAE4.0),and the clinical features and therapies were summarized.Results There were 160 cases aged from 36 to 78 in our study,including 92 male patients and 68 female patients.Non-small cell lung cancer(56.3%)was the most common cancer in our study.Most patients develop skin and mucosal reactions after targeted therapy of EGFRIs in one to three weeks.Skin and mucosal lesions included acne-like rash(n=124,77.5%),xerosis(n=85,53.1%),erythema desquamation(n=38,23.8%),paronychia and pyogenic granuloma-like lesions(n=34,21.3%),hair changes(n=27,16.9%)and oral mucositis(n=13,8.1%).The severity of lesions was one to two grades in 106 patients,and≥three grades in 54 patients.After two to four weeks of appropriate treatments,the adverse reactions of most patients were controlled,while six patients were controlled by reducing the dose of EGFRIs and nine patients were controlled by discontinuing targeted therapy.Conclusion The most common skin and mucosal reaction caused by EGFRIs is acne-like rash,followed by xerosis.Most skin rashes are mild to moderate,which could be relieved by appropriate treatments,reduction of dosage or discontinuation of EGFRIs.