Efficacy And Safety Of Apatinib Mesylate In The Treatment Of Advanced Hepatocellular Carcinoma Associated With HBV

Objective:The purpose of this study was to evaluate the clinical efficacy and adverse reaction of apatinib mesylate for the patients with advanced hepatocellular carcinoma associated with HBV.Method:Clinical data of 37 patients with HBV-associated advanced hepatocellular carcinoma who received the treatment of apatinib mesylate in the first affiliated hospital of Bengbu Medical College from January 2015 to May 2017 were collected.The treatment dose of apatinib mesylate was 500mg/day.or 250mg/day reduced due to grade 3/4 adverse reactions until progressive disease(PD)or no adverse reaction tolerated,combined with entecavir 0.5mg/day.The primary endpoint was progression free survival(PFS),and the secondary endpoints included overall survival(OS),objective response rate(ORR),disease control rate(DCR),and adverse events.Modified Response Evaluation Criteria in Solid Tumors(mRECIST)and National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0(NCI CTCAE 4.0)were used to evaluate clinical efficacy and adverse events respectively.The survival rate was estimated by kaplan-meier method,and median survival time was calculated.Result:By the last follow-up,37 patients had died,with median FPS 2.7 months and median OS 6.4 months.Stratified analysis showed that median PFS and median OS in the TACE treatment failure group was longer than that of the FOLFOX4 treatment failure group and the sorafenib treatment failure group.ORR and DCR were respectively 8.11%(3/37)and 51.35%(19/37).After 2 cycles of treatment,KPS was significantly improved and the clinical symptom improvement rate was 62.16%(23/37).After 2 cycles of treatment,AFP level was(1096.68±285.46)μg/L,which was statistically significant compared with that before treatment(P<0.05).The apatinib-related adverse events were common,which include increased bilirubin 59.46%、increased AST/ALT 59.46%、high blood pressure 48.65%、proteinuria 45.95%、hand and foot syndrome(HFSR)40.54%、anorexia 43.24%、fatigue 24.32%、neutropenia 32.43%and thrombocytopenia 27.03%.However,most of them were mild or moderate adverse reactions,which could be tolerated andcontrolled by patients.The apatinib-related grade 3/4 adverse events were HFSR 8.11%、hypertension 5.41%、neutropenia 2.70%、thrombocytopenia5.41%、increased AST/ALT 5.41%、increased bilirubin 8.11%、fatigue 2.70%and upper gastrointestinal bleeding 2.70%.Among them,grade 4 adverse reactions were hypertension crisis 2.70%and life-threatening severe upper gastrointestinal bleeding 2.70%.No grade 5 adverse events occurred.Conclusion:Apatinib mesylate is effective and safe in the therapy of the patients with advanced hepatocellular carcinoma associated with HBV,who have a good tolerance to the adverse reactions.