非小细胞肺癌患者贝伐珠单抗相关不良反应临床分析

Clinical analysis of bevacizumab-related adverse reactions in patients with non-small cell lung cancer

目的探讨贝伐珠单抗(Bev)治疗非小细胞肺癌(NSCLC)致不良反应的发生情况及其特点。方法收集2019年5月至2021年3月在亳州市中医院呼吸内科接受Bev治疗的NSCLC患者病历资料,筛选出经Naranjo评分法判定为发生Bev相关不良反应者,从病历中提取相关信息,就不良反应发生情况(发生率、发生时间、临床表现、严重程度等)及其转归进行回顾性分析。Bev用药方案为7.5 mg/kg静脉滴注、1次/21 d(1个周期)。结果纳入分析的患者为142例,接受Bev治疗1、2、3、4、5个周期者分别为17例(12.0%)、20例(14.1%)、51例(35.9%)、35例(24.6%)和19例(13.4%)。所有患者均联用了传统化疗药物,其中联合培美曲塞、培美曲塞+卡铂和培美曲塞+顺铂者分别为10例(7.0%)、41例(28.9%)和91例(64.1%)。142例患者中49例(34.5%)发生不良反应,严重程度分级为1、2、3、4级者分别为18、19、6、6例,≥3级严重不良反应发生率为8.5%(12/142)。不良反应表现为血液系统损伤者12例(8.5%,1级4例,2级8例),高血压11例(7.7%,1级4例,2级3例,3、4级各2例),皮肤损伤8例(5.6%,2级5例,3级3例),出血事件6例(4.2%,1级3例,3级1例,4级2例),胃肠道反应6例(4.2%,1、2级各3例),蛋白尿3例(2.1%,均1级),肺动脉栓塞1例(0.7%,4级),胃穿孔1例(0.7%,4级),脱发1例(0.7%,1级)。发生1~2级不良反应的37例患者未停用Bev,其中25例给予对症治疗;发生≥3级不良反应的患者均停用Bev并给予对症治疗;所有患者均痊愈或好转。结论Bev治疗NSCLC的常见不良反应包括血液系统损伤、高血压、皮肤损伤、出血事件、胃肠道反应和蛋白尿,严重程度多为1~2级;偶见肺动脉栓塞、胃穿孔等严重不良反应。≥3级不良反应患者停用Bev并给予对症治疗,预后较好。

Objective To explore the occurrence and characteristics of adverse reactions related to bevacizumab(Bev)in treatment of non⁃small cell lung cancer(NSCLC).Methods The medical records of NSCLC patients treated with Bev in the Respiratory Department of Bozhou Hospital of Traditional Chinese Medicine from May 2019 to March 2021 were collected.Patients with Bev⁃related adverse reactions,which were judged by Naranjo scoring method,were selected.The relevant information in these patients was extracted from their medical records,and the occurrence and outcomes of the adverse reactions(incidence,time of occurrence,clinical manifestation,severity,etc.)were analyzed retrospectively.The dosing regimen of Bev was IV infusion of 7.5 mg/kg once per 21 days(1 cycle).Results A total of 142 patients were included in the analysis,and 17(12.0%),20(14.1%),51(35.9%),35(24.6%),and 19(13.4%)patients received 1,2,3,4,and 5 cycles of Bev treatment,respectively.All patients were treated with combination regimen with traditional chemotherapy drugs,including pemetrexed in 10 patients(7.0%),pemetrexed+carboplatin in 41 patients(28.9%),and pemetrexed+cisplatin in 91(64.1%)patients,respectively.Among the 142 patients,49(34.5%)had adverse reactions,which were classified as grade 1,2,3,and 4 in severity in 18,19,6,6 patients respectively,and the incidence of serious adverse reactions(≥grade 3)was 8.5%(12/142).The clinical manifestations of adverse reactions included hematologic injury in 12 patients(8.5%;grade 1 in 4 and grade 2 in 8 patients),hypertension in 11 patients(7.7%;grade 1 in 4,grade 2 in 3,grade 3 in 2,and grade 4 in 2 patients),skin injury in 8 patients(5.6%;grade 2 in 5 and grade 3 in 3 patients),bleeding events in 6 patients(4.2%;grade 1 in 3,grade 3 in 1,and grade 4 in 2 patients),gastrointestinal reaction in 6 patients(4.2%;grade 1 in 3 and grade 2 in 3 patients),proteinuria in 3 patients(2.1%,grade 1),pulmonary embolism in 1 patient(0.7%,grade 4),gastric perforation in 1 patient(0.7%,grade 4),and alopecia in 1 patient(0.7%,grade 1).Bev was not discontinued in 37 patients who developed grade 1⁃2 adverse events,and 25 of them were given symptomatic treatments.Patients with grade≥3 adverse reactions stopped Bev and received symptomatic treatments.All patients recovered or were improved.Conclusions The common adverse reactions in Bev treatment for NSCLC include hematologic injury,hypertension,skin injury,bleeding events,gastrointestinal reaction,and proteinuria,most of which are of grade 1⁃2 in severity.Severe adverse effects such as pulmonary embolism and gastric perforation occurred occasionally.Patients with grade≥3 adverse reactions have a good prognosis when Bev is discontinued and symptomatic treatments are given.