安罗替尼联合化疗治疗晚期平滑肌肉瘤的回顾性研究

A single-center retrospective study of the patients with advanced or metastatic leiomyosarcoma in the treatment of anlotinib combined with chemotherapy

目的评价安罗替尼联合化疗治疗不可手术切除的局部晚期或转移性平滑肌肉瘤的疗效和安全性。方法回顾性分析2018—2019年间本中心接受安罗替尼联合化疗治疗的晚期平滑肌肉瘤患者的客观缓解率、生存率及不良反应。化疗分为DE方案(达卡巴嗪+表柔比星)和非DE方案,后者包括表柔比星、吉西他滨、多西他赛和异环磷酰胺等。根据实体瘤疗效评价标准1.1版评估近期疗效,同时还记录了不良事件。结果共入组患者43例,其中男6例,女37例,中位年龄51岁;一线治疗34例,二线治疗9例。中位随访时间16个月。客观缓解率为19%,疾病控制率为88%,中位无进展生存期为8.8个月,24周无进展生存率为65%,1年总生存率为86%。单因素分析显示年龄、原发部位、FNCLCC分级、一线或二线治疗、DE方案与非DE方案对中位无进展生存期无影响(均P>0.05)。常见不良反应包括骨髓抑制、恶心、呕吐、高血压和口腔黏膜炎等,以1~2级为主,4例出现中性粒细胞缺乏伴发热。无治疗相关死亡。结论安罗替尼联合化疗治疗晚期平滑肌肉瘤的客观缓解率未见明显提高,但疾病控制率和近期生存率令人满意,不良反应可耐受,值得进一步开展前瞻性临床研究。

Objective To evaluate the efficacy and safety of the combination treatment with anlotinib and chemotherapy in patients with unresectable locally advanced or metastatic leiomyosarcoma.Methods We retrospectively analyzed the overall response rate(ORR),progression-free survival(PFS),PFS at 24 weeks,1-year survival rate and adverse events of patients with advanced leiomyosarcoma in the treatment of anlotinib combined with chemotherapy in our center from January 2018 to December 2019.Meanwhile,the factors associated with efficacy were explored.The chemotherapy regimens were classified into dacarbazine plus epirubicin(DE)and the others(non DE),including epirubicin and/or gemcitabine,docetaxel,ifosfamide and so on.The short-term efficacy was assessed according to RECIST 1.1.Meanwhile,adverse events were recorded.Results Among 43 patients in this cohort,6 males and 37 females with a median age of 51 years recieved first-line therapy in 34 patients and second-line in 9 cases.The median follow-up time was 16 months.The ORR was 19%,with a DCR of 88%.The median PFS was 8.8 months,and the PFS at 24 weeks was 65%.The 1-year survival rate was 86%.Univariate analysis showed that there was no significant difference in median PFS among different subgroups,including age,primary site,FNCLCC classification and the lines and regimens of therapy.The common treatment-related adverse events were bone marrow suppression,nausea,vomiting,hypertension and oral mucositis,which was mainly at grade 1 to 2.Only 4 patients had severe adverse event,which was febrile neutropenia.No treatment-related death was observed.Conclusions The ORR of anlotinib combined with chemotherapy in the treatment of patients with advanced leiomyosarcoma was not significantly improved.However,the DCR,the median PFS and the 1-year survival rate were satisfactory.The adverse reactions were tolerable.Further prospective clinical studies are warranted.