114例神经母细胞瘤患儿13-顺式维甲酸维持治疗用药安全性观察

Safety observation of 13-cis retinoic acid maintenance therapy in 114 children with neuroblastoma

目的评价13-顺式维甲酸(13-CRA)的安全性,为临床安全有效地使用该药提供依据。方法连续纳入应用维甲酸维持治疗神经母细胞瘤(NB)患儿,采用问卷调查法收集NB患儿在13-CRA用药期间,发生的任何不良事件,判断不良事件与药物的关系,并计算不良反应发生率。结果2018年3月-12月期间,共纳入114名NB患儿,男65例,女49例,年龄11个月~14岁,中位年龄4岁5个月。其中高危组94例,中危组20例,原发瘤灶为腹膜后及肾上腺区76例,后纵膈38例。患儿服用13-CRA剂量160mg/(m^2·d),分两次,连用14d停14d为1个周期,共6~12个周期。总体药物不良反应发生率为100%,其中轻度60例(52.6%),中度36例(31.6%),重度18例(15.8%),无严重不良反应发生。不良反应主要涉及皮肤黏膜系统(114例,100%),其他可见于肌肉骨骼系统(14例,12.3%)、消化系统(18例,15.8%)、神经精神系统(9例,7.9%)及血液系统(6例,5.3%)。结论13-CRA用于NB患儿维持治疗总体药物安全性较好,药物不良反应以皮肤干燥为主,当前剂量疗程下患儿可耐受。

Objective To evaluate the safety of 13-cis Retinoic acid(13-CRA)and provide a reference for clinical safe and effective use of the medication.Methods Neuroblastoma(NB)patients in maintenance therapy with 13-CRA were continuously enrolled.Questionnaires were used to collect any adverse reactions during the maintenance therapy,which help to determine the relationship between adverse reactions and 13-CRA,and calculate the incidence.Results From March to December 2018,114 children with NB were enrolled,including 65 males and 49 females,aged from 11 months to 14 years,with a median age of 4 years 5 months.Among them,94 were in high-risk group and 20 in mederate-risk group.The primary tumor in 76 cases were retroperitoneal and adrenal gland,and in 38 cases was posterior mediastinum.The 13-CRA 160 mg/(m 2·d)in two divided doses was provided for 14 days in every 28 days for total 6-12 cycles.The overall adverse drug reaction rate was 100%,including mild(grade 1)60 cases(52.6%),moderate(grade 2)36 cases(31.6%),and severe(grade 3)18 cases(15.8%).No serious adverse(grade 4)reaction occurred.Adverse reactions mainly involved skin mucosal system(114 cases,100%).Others were found in the musculoskeletal system(14 cases,12.3%),digestive system(18 cases,15.8%),neuropsychiatric system(9 cases,7.9%)and blood system(6 cases,5.3%).Conclusions 13-CRA is safe for the treatment of children with NB.The adverse drug reactions are mainly presented as dry skins.The children can tolerate under current dose treatment.