沙利度胺缓解阿帕替尼治疗骨与软组织肉瘤不良反应的回顾性研究

Efficacy of thalidomide in alleviating adverse reactions induced by apatinib in bone and soft-tissue carcinoma: a retrospective cohort study

目的探索具有抗血管生成诱导血管正常化、抗炎、免疫调节作用的沙利度胺是否能够减轻VEGFR-TKI阿帕替尼的不良反应。方法本研究回顾性分析54例骨与软组织肉瘤患者,分为两组,接受阿帕替尼单药500 mg每天1次和沙利度胺100 mg每晚1次联合阿帕替尼500 mg每天1次治疗各27例,根据CTCAE 5.0评价药物不良反应,对比两组患者不良反应。结果总不良反应率:对照组为32.51%,实验组为15.23%,差异有统计学意义(P<0.001)。Ⅲ级及以上不良事件总发生率:对照组为2.26%,实验组为0%,差异有统计学意义(P<0.001)。白细胞减少:对照组48.15%,实验组18.52%,差异有统计学意义(P=0.020);对照组Ⅲ级及以上不良反应7.41%。血小板减少:对照组25.93%,实验组3.70%,差异有统计学意义(P=0.023);对照组Ⅲ级及以上不良反应率3.70%。腹泻:对照组40.74%,实验组14.81%,差异有统计学意义(P=0.036)。蛋白尿:对照组74.07%,实验组29.63%;差异有统计学意义(P=0.001);对照组Ⅲ级及以上不良反应率7.41%。手足综合征:对照组62.96%,实验组33.33%;差异有统计学意义(P=0.015);对照组Ⅲ级及以上的不良反应率为14.81%。结论沙利度胺能有效缓解阿帕替尼引起的腹泻、肾功能不良、蛋白尿等不良反应,提高患者对药物的耐受性。

Objective To explore whether thalidomide,a drug which has antiangiogenic,anti-inflammatory and immunomodulatory properties,can alleviate the adverse reactions induced by apatinib.Methods A retrospective analysis on 54 cases with bone and soft-tissue carcinoma was conducted.All were divided into two groups.Control group (n=27) was given apatinib monotherapy at the dose of 500 mg qd,while treatment group (n=27) was given combined treatment of apatinib (500 mg qd) and thalidomide (100 mg qn).Adverse reactions were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.Results Incidences of total adverse effects (AEs) showed significant differences between the control (32.51%) and treatment (15.23%) group (P < 0.001).Total grade 3 / 4 AEs of control group were more than those of treatment group (2.26% vs.0%,P < 0.001).Significance differences in leukopenia,thrombocytopenia,diarrhoea,proteinuria and hand-foot syndrome were shown between the two groups (48.15% vs.18.52%,P=0.020;25.93% vs.3.70%,P=0.023;40.74% vs.14.81%,P=0.036;74.07% vs.29.63%,P=0.001;62.96% vs.33.33%,P=0.015).Furthermore,grade 3 / 4 AEs of leukopenia,thrombocytopenia,proteinuria and hand-foot syndrome were observed in the control group (7.41%,3.70%,7.41%,14.81%,respectively),but not in the treatment group.Conclusions Thalidomide can effectively relieve the adverse reactions such as diarrhea,renal insufficiency and proteinuria after apatinib treatment,which will improve the tolerance of treatment significantly.