表皮生长因子受体抑制剂相关性皮肤毒性的研究进展

Advance of the mechanism and treatment options for cutaneous toxicities induced by epidermal growth factor receptor inhibitors

关键词:  表皮生长因子受体抑制剂  痤疮样皮疹  临床试验  维生素K  四环素类

Key words:  EGFR inhibitor  acne-like skin rash  clinical trials  vitamin K  tetracyclines

摘要:

表皮生长因子受体抑制剂包括小分子酪氨酸激酶抑制剂及单抗类，在肺癌、结直肠癌等肿瘤的分子靶向治疗中起着重要作用。其中小分子酪氨酸激酶抑制剂包括吉非替尼、厄洛替尼、埃克替尼等，单抗类包括西妥昔单抗、帕尼单抗等。以痤疮样皮疹为代表的皮肤毒性是表皮生长因子受体抑制剂使用后最常见的不良反应，严重的皮肤毒性导致药物剂量减少与治疗的中断，影响药物的抗肿瘤疗效。但目前临床对于这一类皮肤毒性仍没有十分有效的处理方法。已有临床试验涉及的处理方法包括口服四环素类药物、局部应用维生素K乳剂、局部应用他克莫司、防晒霜以及表皮生长因子凝胶等。本文综述了此类皮疹的发生机制、治疗皮疹药物的临床试验结果及已有的专家共识或指南，以期为这一类不良反应的处理提供临床思路。

Abstract:

Epidermal growth factor receptor (EGFR) inhibitors include small molecule tyrosine kinase inhibitors and monoclonal antibodies, which play an important role in the targeting therapies of lung cancer and colorectal cancer, etc. Among them, the small molecule tyrosine kinase inhibitors include gefitinib, erlotinib, icotinib, etc, while monoclonal antibodies include cetuximab and panitumumab. The cutaneous toxicities, often described as acne-like rash, were the most common side-effects observed during EGFR targeted treatment. The severe skin toxicity may induce dose reduction or interruption of treatment, and thus reducing the anti-tumor effect. However, there is still no effective treatment for management of skin toxicity. Current clinical trials have evaluated the managements including oral tetracycline drugs, local application of vitamin K cream, local application of tacrolimus, sunscreen and epidermal growth factor gel. In this review, the mechanism of occurrence, the results of the current trails about the treatment for such skin toxicity, and the available expert consensus and guidance are discussed, so as to provide thoughts for the clinical practice.