阿法替尼皮肤不良反应及其与疗效的相关性分析

【摘要】 目的 探讨阿法替尼治疗肺癌引起的皮肤不良反应类型和严重程度及其与抗肺癌疗效的相关性。方法 对2016年12月至2018年1月在东南大学附属中大医院使用阿法替尼治疗的肺癌患者进行病例-病例对照研究。根据国际肿瘤化疗药物不良反应评价系统4.0标准评估76例肺癌患者皮肤不良反应的类型及严重程度，按皮疹的严重程度分0级、1级、2级以上皮疹组。患者每隔3个月行胸部CT检查，根据实体肿瘤的疗效评价标准评估阿法替尼的抗肺癌疗效。采用Kruskal-Wallis H test秩和检验比较不同等级皮疹患者阿法替尼的抗肺癌疗效。结果 76例肺癌患者中，44例疾病稳定或部分缓解，32例疾病进展。69例出现皮肤不良反应，包括42例（55.3%）痤疮样皮疹、35例（46.1%）甲沟炎、30例（39%）黏膜糜烂、8例（10.5%）毛发改变、6例（7.9%）手足综合征。0级皮疹组7例，有效3例；1级皮疹组19例，有效7例；2级以上皮疹组50例，有效34例，3组有效率差异有统计学意义（χ2 = 6.117，P = 0.047），1级与2级以上皮疹组的有效率均高于0级组（均P < 0.001），2级以上皮疹组的有效率高于1级组（P < 0.001）。结论 阿法替尼治疗肺癌可引起痤疮样皮疹、甲沟炎、黏膜糜烂、毛发改变和手足综合征等不同类型皮疹，皮疹的严重程度分级越高，阿法替尼的抗肺癌疗效越显著。

Skin adverse reactions to afatinib and their correlation with anti-lung cancer efficacy

Objective To investigate the type and severity of skin adverse reactions induced by afatinib in the treatment of lung cancer,and to analyze their correlation with anti-lung cancer efficacy.Methods A case-case-control study was conducted on lung cancer patients treated with afatinib in ZhongDa Hospital,Southeast University from December 2016 to January 2018.The type and severity of skin adverse reactions were evaluated in 76 patients with lung cancer based on the National Cancer Institute-Common Terminology Criteria for Adverse Events(NCI-CTCAE)Version 4.0,and these patients were divided into 3 groups according to the severity of skin lesions,including grade-0,-1,and-2/3 groups.The patients underwent chest computed tomography(CT)examination every 3 months,and the tumor response to afatinib was evaluated according to the Response Evaluation Criteria in Solid Tumors(RECIST).Anti-lung cancer efficacy of afatinib was compared among the patients with different grades of skin lesions by using the Kruskal-wallis H rank sum test.Results After treatment with afatinib,44 of the 76 patients with lung cancer achieved stable condition or partial remission,and 32 experienced disease progression.Skin adverse reactions occurred in 69 patients,and manifested as acneiform lesions in 42(55.3%)patients,paronychia in 35(46.1%),mucosal erosions in 30(39%),hair changes in 8(10.5%),and hand-foot syndrome in 6(7.9%).Improvement was achieved in 3,7 and 34 cases in the grade-0,-1,and-2/3 groups(n=7,19 and 50 respectively),respectively.There was a significant difference in the response rate among the 3 groups(χ2=6.117,P=0.047),and the response rate was significantly higher in the grade-1 and-2/3 groups than in the grade-0 group(both P<0.001),and higher in the grade-2/3 group than in the grade-1 group(P<0.001).Conclusion The treatment of lung cancer with afatinib can cause various types of skin lesions,such as acneiform lesions,paronychia,mucosal erosions,hair changes and hand-foot syndrome,and the higher the severity of the skin lesions,the more marked the anti-lung cancer efficacy of afatinib.