达拉非尼联合曲美替尼在黑色素瘤治疗中致皮肤系统不良反应的文献分析

Literature analysis of dermal system adverse reactions caused by dabrafenib and trametinib in melanoma patients

目的:分析达拉非尼联合曲美替尼治疗黑色素瘤致皮肤系统不良反应(ADR)的发生情况及临床特点,为临床安全用药提供参考。方法:检索Web of Science、PubMed、知网和万方数据库,收集国内外相关个案报道并进行分析总结。结果:共筛选出有效文献31篇,共38例次,患者年龄主要为31~80岁(89.47%);ADR多发生在用药后90 d内(60.52%);主要临床表现为痤疮样皮疹(18.42%)、肉芽肿性皮炎(13.16%)、脂膜炎(10.53%)、纹身并发症(10.53%)及结节性红斑病变(10.53%);34例患者皮肤ADR痊愈或好转,其中2例永久停用了达拉非尼与曲美替尼,10例继续联合治疗,12例暂停联合治疗,其中11例患者好转或痊愈后重启联合治疗。在重启或继续使用联合治疗的患者中,10例再次出现ADR。结论:本研究中,达拉非尼联合曲美替尼致皮肤系统ADR表现出不同的发生率和特征,且免疫治疗后进行靶向治疗可能增加严重皮肤ADR发生风险。临床在联合使用时应加强用药监测,及时发现ADR并采取适当的防治措施,同时严密监测重启或继续用药所致ADR,确保用药安全。

Objective:To analyze the occurrence and clinical characteristics of adverse drug reaction(ADR)in dermal system caused by dabrafenib and trametinib in melanoma patients,and provide references for clinical safety drug use.Methods:Case reports of dermal system ADR induced by dabrafenib and trametinib in melanoma patients retrieved from Web of Science,PubMed,China national knowledge infrastructure(CNKI)and Wangfang database were analyzed and summarized.Results:A total of 31 literatures including 38 cases were included.Most patients aged 31–80 years old(89.47%).Most ADRs occurred within 90 days after medication(60.52%),the main clinical manifestations of which were acne-like rash(18.42%),granulomatous dermatitis(13.16%),adipositis(10.53%),tattoo complications(10.53%)and erythema nodosum(10.53%).Dermal ADR recovered or improved in 34 patients,including 2 patients permanently discontinued dabrafenib and trametinib,ten patients continued the combination therapy,and 12 patients temporarily discontinued the combination therapy at the onset of ADR.11 patients resumed the combination therapy after the ADR improved or recovered.10 paitents who resumed or continued the combination therapy developed dermal ADR again.Conclusion:In this study,dermal ADR induced by dabrafenib combined with trametinib showed different incidence and characteristics.Targeted therapy followed by immunotherapy might increase the risk of severe dermal ADR.When using dabrafenib combined with trametinib,it is necessary to closely monitor ADR,especially for the patients restarting of continuing the combination therapy,timely recognize relevant ADR and give appropriate prevention and treatment measures,thus to ensure the safety of medication.