安罗替尼单药或联合替吉奥治疗索拉非尼耐药晚期肝细胞癌疗效研究

Observation on Effect of single anlotinib or combined with tegafur in treating sorafenib resistant advanced hepatocellular carcinoma

目的观察安罗替尼(ANL)单药或联合替吉奥(S1)治疗索拉非尼耐药晚期肝细胞癌(HCC)的疗效和不良反应。方法选取2018年8月至2019年6月该院收治的经索拉非尼治疗无效或进展HCC患者20例,采用随机数字表法分为ANL组和ANL+S1组,每组10例。ANL组口服ANL 12 mg,每天1次,连续服用14 d,停用1周,每21天重复。ANL+S1组口服ANL 12 mg,每天1次,S140 mg,每天2次,两药均连续服用14 d,停用1周,每21天重复。2组患者均用药至疾病进展或发生不能耐受的不良反应为止。发生不能耐受的不良反应患者根据情况将ANL剂量降至每天10 mg或每天8 mg。每6周复查CT评价疗效。结果ANL组患者中部分缓解1例,稳定5例,进展(PD)4例,总有效率(ORR)为10.0%(1/10),疾病控制率(DCR)为60.0%(6/10),PD率为40.0%(4/10),无进展生存时间(PFS)和总生存期(OS)分别为3.0、6.0个月(95%可信区间:0.7~5.3、4.7~7.3)。ANL+S1组患者中部分缓解2例,稳定5例,PD 3例,ORR为20.0%(2/10),DCR为70.0%(7/10),PD率为30.0%(3/10),PFS和OS分别为4.5、7.5个月(95%可信区间:3.6~5.4、6.5~8.5)。2组患者ORR、DCR比较,差异均无统计学意义(P>0.05);2组患者PFS、OS比较,差异均有统计学意义(P<0.05)。不良反应主要为疲劳、食欲减退和高血压。结论对索拉非尼治疗耐药晚期HCC给予ANL单药治疗有效,不良反应可耐受。ANL联合S1治疗可延长患者的PFS和OS。

Objective To observe the efficacy and adverse reactions of single anlotinib(ANL)or combined with tegafur(S1)in treating sorafenib resistant advanced hepatocellular carcinoma(HCC).Methods Twenty cases of HCC which failure or progress after treatment in this hospital from August 2018 to June 2019 were selected and divided into the ANL group and ANL+S1 group according to the random number table method,qo cases in each group.The ANL group orally took 12 mg anlotinib once a day for 14 d consecutive,with 1 week of discontinuation,and repeated every 21 d.The ANL+S1 group received oral 12 mg anlotinib once a day and 40 mg S1 twice daily for 14 d consecutive,with 1 week of discontinuation,and repeated every 21 d.All cases used the medication until disease progression or intolerance of adverse reactions.For the patients with intolerance to adverse reactions,the ANL dose was reduced to 10 mg or 8 mg per day according to the patient′condition.CT was reviewed every 6 weeks to evaluate the efficacy.Results In ANL group:PR in 1 case,SD in 5 cases,PD in 4 cases,the overall response rate(ORR)10.0%(1/10),disease control rate(DCR)60.0%(6/10),PD 40.0%(4/10),progression free survival(PFS)and overall survival(OS)3.0 months(95%CI:0.7-5.3)and 6.0 months(95%CI:4.7-7.3)respectively.In the ANL+S1 group,PR in 2 cases,SD in 5 cases,PD in 3 cases,ORR 20.0%(2/10),DCR 70.0%(7/10),PD 30.0%(3/10),PFS and OS were 4.5 months(95%CI:3.6-5.4)and 7.5 months(95%CI:6.5-8.5),respectively.Comparison of ORR and DCR showed no statistical difference between the two groups.The comparison of PFS and OS showed a statistically significant difference between the two groups(P<0.05).The main adverse reactions were fatigue,loss of appetite and high blood pressure.Conclusion In the treatment of sorafenib-resistant advanced HCC,single ANL is effective and its adverse reactions can be tolerated.ANL combined with S1 may prolongs PFS and OS in the patients.