外用维生素K防治靶向表皮生长因子受体单抗相关性皮疹有效性和安全性系统评价

Systematic Review of the Effectiveness and Safety of External Use of Vitamin K in the Prevention and Treatment of Anti-Epidermal Growth Factor Receptor Monoclonal Antibody-Related Skin Rashes

目的系统评价外用维生素K预防和治疗靶向表皮生长因子受体(EGFR)单抗相关性皮疹的有效性和安全性。方法检索PubMed、Embase、The Cochrane Library、Web of Science、中国知网、维普和万方数据库,检索时限为各数据库自建库起至2022年4月。筛选文献、提取数据,评价文献质量,对结果数据进行描述性分析或采用RevMan 5.3软件进行Meta分析。结果纳入12项研究。涉及的EGFR单抗主要为西妥昔单抗,外用维生素K的剂型主要是乳膏,给药方法多为浓度0.05%~0.1%的维生素K每天外用1次或2次,大部分研究所用维生素K亚型为K1。3项对照试验的Meta分析结果显示,相比对照组,试验组≥2级皮疹的发生率未显著降低[RR=1.18,95%CI(0.96,1.45),P=0.12],同时凝血功能异常及其他皮肤不良事件发生率也无显著差异;除3项对照试验外,纳入的病例系列结论虽均认为外用维生素K可降低≥2级皮疹的发生率,并缩短皮疹持续时间,但以上研究未设置对照组,不能排除外用制剂中保湿剂等辅料的保护作用。结论当前证据表明,浓度0.05%~0.1%的维生素K每天外用1次或2次预防和治疗靶向EGFR单抗相关性皮疹有效性不明确,也未见额外的安全性问题。未来需在维生素K给药剂量、频次、人群分层等方面进一步探索。

Objective To systematically evaluate the effectiveness and safety of external use of vitamin K in the prevention and treatment of anti-epidermal growth factor receptor(EGFR)monoclonal antibody-related skin rashes.Methods Relevant literature in the PubMed,Embase,The Cochrane Library,Web of Science,CNKI,VIP and WanFang databases from the inception of each database to April 2022 was searched and screened,the data were extracted,and the quality of literature was evaluated.Descriptive analysis or Meta-analysis(by RevMan 5.3 software)was performed on the obtained data.Results Twelve studies were included.The involved EGFR monoclonal antibody was mainly cetuximab,the dosage form of vitamin K for external use was mainly cream preparation,the administration method was mostly externall use of vitamin K with a concentration of 0.05%to 0.1%once or twice a day,and the subtype in most studies was vitamin K1.The Meta-analysis of three controlled trials showed that the incidence of skin rashes(≥grade 2)in the test group was not significantly lower than that in the control group[RR=1.18,95%CI(0.96,1.45),P=0.12],and the incidence of abnormal coagulation function and other skin adverse events in the test group was similar to that in the control group.The non-controlled trials showed that the external use of vitamin K could decrease the incidence of skin rashes(≥grade 2)and shorten the duration of skin rashes,but there was no control group in the above studies,so the protective effect of moisturizers and other excipients in formulations for external use could not be ruled out.Conclusion Current evidence indicates that the efficacy of external use of vitamin K with a concentration of 0.05%to 0.1%once or twice a day to prevent and treat anti-EGFR monoclonal antibody-related skin rashes was unclear,and no additional safety concern raised.More exploration is needed in terms of dosage,administration frequency and population stratification of vitamin K in the future.