阿帕替尼致手足综合征临床及文献病例分析

Clinical and literature case analysis of hand-foot syndrome induced by apatinib

目的探讨阿帕替尼相关手足综合征(HFS)的临床特点。方法检索PubMed、维普、中国知网和万方数据库(截至2019年3月20日),收集阿帕替尼相关HFS文献病例报告,加上开滦总医院收治的2例病例,分析该药致HFS的临床特点。结果共收集到16例患者,男性9例,女性7例;年龄(62±16)岁;胃-贲门癌4例,肺癌4例,卵巢癌2例,甲状腺癌2例,其他恶性肿瘤4例;单用阿帕替尼者11例,联用其他抗肿瘤药物者5例;阿帕替尼剂量为850 mg/d者3例,500 mg/d者6例,425 mg/d者1例,250 mg/d者6例(其中2例分别在用药1、2周后增至500 mg/d);HFS分级为1级者2例(12.5%),2级者6例(37.5%),3级者8例(50.0%)。除1例患者应用阿帕替尼至发生HFS的时间不详外,其他15例患者应用阿帕替尼至发生HFS的中位时间为3(1,11)周,其中10例(66.7%)在使用阿帕替尼3周内发病。5例患者除手足皮肤病变外还出现肛周、生殖器、腋窝、腹股沟或口腔等部位皮肤黏膜损害。16例患者中13例还发生了其他不良事件,其中发生高血压者10例(62.5%)。8例1~2级HFS患者经对症治疗症状大多好转或可以耐受,其中3例对阿帕替尼治疗无影响,4例经减量或暂停阿帕替尼后再次服用,患者可耐受,仅1例停药;8例3级HFS的患者对症治疗效果差,其中4例因HFS症状严重停用阿帕替尼,3例死亡。结论阿帕替尼所致HFS多发生在用药后3周内,除可引起手足皮肤病变外还可累及全身多个部位,多伴发高血压;多数患者出现HFS后给予对症处理、合理减量或停药后症状可缓解。

Objective To explore the clinical characteristics of hand-foot syndrome(HFS)induced by apatinib.Methods Case reports of HFS induced by apatinib were collected through searching PubMed,VIP,CNKI,and Wanfang databases(up to March 20,2019).The clinical characteristics of HFS induced by apatinib were analyzed according to the literature above and the information from 2 related patients admitted to Kailuan General Hospital.Results A total of 16 patients were enrolled in the study,including 9 males and 7 females,aged(62±16)years.Apatinib was applied for gastric cardia cancer in 4 patients,lung cancer in 4 patients,ovarian cancer in 2 patients,thyroid cancer in 2 patients,and other malignant tumors in 4 patients.And it was used alone in 11 patients and in combination with other antineoplastic agents in 5 patients.Dosages of apatinib included 850 mg/d in 3 patients,500 mg/d in 6 patients,425 mg/d in 1 patient,and 250 mg/d in 6 patients(the dose was increased to 500 mg/d in 2 patients after 1 and 2 weeks of administration,respectively).According to the severity,HFS was classified as grade 1 in 2 patients(12.5%),grade 2 in 6 patients(37.5%),and grade 3 in 8 patients(50.0%).Except that the time from application of apatinib to HFS occurrence was not known in 1 patient,the median time from medication to HFS occurrence was 3(1-11)weeks in other 15 patients,and 10(66.7%)of them developed HFS within 3 weeks of administration.In addition to the skin lesions of HFS,the skin/mucous membrane damage also appeared on perianal area,genital,axillary fossa,groin,and mouth in 5 patients.Among the 16 patients,13 had other adverse events,including hypertension in 10 patients(62.5%).The symptoms of 8 patients with HFS of grade 1-2 mostly improved or were tolerable after symptomatic treatments.And in detail,3 patients′symptoms had no effect on the treatment of apatinib,4 patients could tolerate a reduced dose or re-medication after a pause,and 1 patient stopped medication.Symptomatic treatment effects were poor in 8 patients with grade 3 HFS,4 of whom stopped apatinib because of the serious HFS and 3 of whom died.Conclusions The HFS induced by apatinib usually occurs within 3 weeks after administration,which can involve many parts of the body except for the skin of hands and feet,and are accompanied with hypertension mostly.HFS symptoms can be relieved by symptomatic treatments,reasonable dose reduction,or drug withdrawal in most patients.