Comparison Of Plasma Concentration And Efficacy Of Apatinib In Patients With Different Child-pugh Grades Of Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma(HCC)is one of the most common malignant tumors in the clinic.The molecular targeted drug apatinib has achieved certain clinical effects in the treatment of hepatocellular carcinoma.The antitumor effect of apatinib and the relationship between adverse reactions and dose,the related preclinical animal experiments,clinical trial research conclusions are different.Most studies have studied the relationship between different doses of apatinib for HCC,ignoring liver function status in the enrolled patients.Studies have shown that apatinib is metabolized by the liver.For patients with different levels of liver function(Child-pugh grade),the relationship between blood concentration,clinical efficacy and adverse reactions after apatinib treatment needs further study.ObjectiveDetecting the plasma concentration of apatinib in patients with different Child-pugh grades of hepatocellular carcinoma,and comparing liver function,solid tumor efficacy and adverse reactions,and exploring different child-pugh grades of hepatocellular carcinoma patients.The effect of patinib metabolism and the differences in clinical efficacy and adverse reactions among patients with different grades guide the rational use of drugs.MethodsA total of 36 patients who met the criteria were included.According to Child-pugh classification combined with Chinese liver cancer staging,they were divided into group A(Child A+IIb),group B1(Child B+IIIa),and group B2(Child B+IIIb).Group A:a total of 15 cases,Group B1:a total of 13 cases,Group B2:a total of 8 cases.There was no significant difference in the age,gender,maximum tumor diameter,hypertension,physical condition score(PS),TACE treatment,and portal vein tumor thrombus(PVTT)among all patients(P>0.05).All patients were orally administered apatinib 250mg/d,and their blood concentrations were measured before the first application of apatinib,9 hours after and 7days after treatment,and the levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)in all patients before and 1 month,3months,and 6 months after administration,and the degree of tumor remission after apatinib treatment in each group was evaluated according to m-RECIST staging and calculated objective response rate(ORR)and disease control rate(DCR).During treatment,monitor the occurrence of adverse reactions in patients.Statistical experimental data were analyzed and compared using SPSS 21.0 software for blood concentration,liver function,solid tumor efficacy and adverse reactions in each group.Results1.After treatment,the average plasma concentration of apatinib in patients in group A at 9h and 7d was 124.95ng/mL and 390.50ng/mL,and the average plasma concentration of apatinib in patients in group B1 at 9h and 7d were 150.07ng/mL and 431.71ng/mL,and the average plasma concentrations of apatinib at 9h and 7d in the B2 group were 174.79ng/mL and 456.90ng/mL,respectively.2.Comparison of ALT,AST and TBIL at four different time points within the three groups of patients(The F values are:371.845,918.764,442.993,P<0.01).There are significant differences in ALT,AST and TBIL levels at different time points in different groups(The F values are:68.654,129.808,94.426,P<0.01).There are significant differences in the changes in the levels of ALT,AST and TBIL(The F values are:2.976,4.503,2.800,P<0.01).3.There are no significant differences in the ORR comparison between the three groups(P>0.05).The comparison of DCR between group A and group B2 was statistically significant(P<0.05).There are no significant differences in the DCR comparison between group A and B1,and between group B1 and B2(P>0.05).4.The difference in the total number of adverse reactions between group A and group B2 and group B1 and group B2 are statistically significant(The?~2 values are:4.189,3.971,P<0.05).The difference between group A and group B1 was significant(P>0.05).There was a statistically significant difference in the total number of grade III-IV adverse reactions between groups A and B2 and groups B1 and B2(?~2=4.373,P<0.05).There was no significant difference between group A and group B1(P>0.05).Conclusion1.In patients with hepatocellular carcinoma treated with apatinib,the higher the Child-pugh grade,the higher the plasma concentration of apatinib in a certain period of time.2.Apatinib improves the liver function of patients with hepatocellular carcinoma and improves the patient's disease control rate and objective remission rate,especially in patients with a lower Child-pugh grade,liver function improvement is more significant,and solid tumors it is good.3.During the treatment with apatinib,the degree of adverse reactions is light,especially in patients with a lower Child-pugh grade,fewer adverse reactions occur and are easy to control.