| Background and ObjectiveHepatocellular carcinoma(HCC)is a malignant tumor occurring in hepatocytes,accounting for at least 90%of Primary hepatic carcinoma(PHC).Cholangiocar-cinoma is a malignant tumor of bile duct cells in the liver.Both belong to PHC.China is a country with a high incidence of PHC,accounting for about 70%of the total PHC incidence in the world.The mortality rate was about 20.37 per 100,000,the second highest among malignancies.According to the Barcelona staging system,patients with advanced portal vein thrombus cancer or extrahepatic metastasis.The incidence of primary liver cancer is occult,with a high degree of malignancy.Most patients have developed to the advanced stage of cancer when diagnosed,and have lost the chance of radical treatment,with a very low 5-year survival rate.Traditional treatment methods have not achieved satisfactory results so far.In the 1990s,with the rapid development of molecular biology and tumor cytology,more and more anti-tumor targeted drugs with the advantages of high selectivity and low toxicity are applied to the treatment of malignant tumors.In 2007,the targeted drug sorafenib was launched,which extended the overall survival of patients with advanced primary liver cancer and opened a new era of PHC treatment.However,due to its characteristics of drug resistance,high price,limited benefit and high toxicity,the search for new targeted drugs never stopped.It was not until the past two years that regorafenib,lenvatinib,cabozantinib and remolumizumab were successively marketed,whose efficacy further confirmed the potential value of molecularly targeted drugs in PHC,especially multi-target drugs.Amlotinib hydrochloride is a novel multi-target tyrosine kinase inhibitor based on sorafenib,which has the dual function of anti-tumor angiogenesis and inhibiting tumor growth.Based on the study results of ALTER 0303,it has been approved by the China food and drug administration(CFDA)for third-line treatment of advanced NSCLC and SCLC patients and second-line treatment of patients with soft tissue sarcoma.Currently,phase ?/? clinical trials are being conducted for gastric cancer,esophageal cancer,kidney cancer,thyroid cancer,colorectal cancer and other malignant tumors.Some studies have shown that amlotinib hydrochloride may inhibit the expression of bcl-2 and Survivin by inhibiting the Erk and Akt pathways,promote the expression of Bax,and may have a direct inhibitory effect on HCC.In vitro studies confirmed the metastasis and invasion of human intrahepatic bile duct cell carcinoma(ICC)cell line hccc-9810.To investigate the clinical efficacy of amlotinib hydrochloride in the treatment of advanced PHC,we designed this study to retrospectively analyze the clinical efficacy,safety and prognostic factors of amlotinib hydrochloride in the treatment of advanced liver cancer.Materials and methodsIn this study,55 patients with advanced primary liver cancer treated with amlotinib hydrochloride who visited our hospital from July 2018 to April 2019 were included,of whom 50(90.9%)were hepatocellular carcinoma(HCC)and 5(9.1%)were hepatocellular carcinoma(HCC).The preliminary follow-up is to collect relevant clinical data of patients through the electronic medical record system,analyze the date when the patients begin treatment and the disease progresses,synchronously record the hematology and imaging results of the patients,and record the adverse reactions of the patients at any time.Follow-up was conducted mainly by telephone,focusing on the follow-up of OS,duration of withdrawal of amlotinib,and follow-up treatment.SPSS23.0 statistical software was used to process data.Kaplan-meier method was used to draw the survival curve.Cox regression analysis was used to analyze the influencing factors affecting the prognosis of patients with advanced liver cancer.Variables with P<0.10 in Cox univariate analysis were included in the multivariate Cox regression analysis,and P<0.05 was considered statistically significant.Result(1)In this study,a total of 55 patients with advanced hepatocellular carcinoma were included,including 42 patients who received amlotinib hydrochloride in the first line and 13 patients who received enrottinib hydrochloride in the second line or above.The median total survival time was 8.5 months(255.0d)and 2.7 months(80.0d)(P=0.032)separately,and the overall population mOS was 8.3 months(95%CI:80.5?415.5).In this study,50 patients with advanced HCC and 5 patients with ICC were included,with mOS at 8.3 months(248.0d)and 10.6 months(318.0d)(P=0.820),respectively,showing no statistical significance.(2)The majority of patients(79.02%)had mild to moderate(grade 1-2)AEs,which could be improved or tolerated by symptomatic treatment,and the total incidence of adverse reactions was 72.73%(40/55).55 patients with high blood pressure is the most common adverse reactions to 28 cases(50.91%)and low platelet count in 16 cases(29.09%),23 cases(21.82%),joint pain,10 cases(18.18%),white blood cell count,reduce 10 cases(18.18%),neutrophil absolute value lower 10 cases(18.18%),9 cases(16.36%),diarrhea,abdominal distension,7 cases(12.73%),loss of appetite,7 cases(12.73%),6 patients with extremities syndrome(10.915);Acuity level 3 AEs,including 7 cases of hypertension(12.73%)and low platelet count in 5 cases(9.09%),fatigue(7.27%),4 cases of absolute value of neutrophil reduce 3 cases(5.45%),white blood cell count,2 cases(3.64%),lower hemoglobin in 2 cases(3.64%),diarrhea in 2 cases(3.64%),syndrome of hand,foot and 1 case(1.82%),joint pain,1 case(1.82%),abdominal distension in 1 case(1.82%),loss of appetite,1 case(1.82%).During the study period,the dosage of 2 patients was reduced to 10mg due to grade 3 hypertension,1 patient's blood pressure was still poorly controlled and the dosage was reduced to 8mg,1 patient was reduced to 10mg due to frequent diarrhea,and no patient was withdrawn due to intolerance.One patient with severe esophageal varices with HCC who received amlotinib hydrochloride for 3 days developed fatal gastrointestinal bleeding,which was a non-drug-related death.(3)Total bilirubin(HR=2.012,P=0.001),albumin(HR=1.452,P=0.047),and combined surgery(HR=1.648,P=0.024)were independent risk factors for the prognosis of advanced HCC.Conclusion(1)Amlotinib hydrochloride has clinical efficacy in the treatment of advanced primary liver cancer,which can prolong the overall survival of patients,and the adverse reactions are controllable and well tolerated,providing a treatment option for patients with advanced liver cancer.(2)Amlotinib hydrochloride has limited benefits in patients with advanced liver cancer who have received systematic treatment before,and can be selected according to the patient's general condition,disease status,economic status,personal will,etc.(3)Total bilirubin(HR=2.012,P=0.001),albumin(HR=1.452,P=0.047),and combined TACE(HR=1.648,P=0.024)before amlotinib hydrochloride treatment were independent risk factors for the prognosis of advanced HCC. |
PDF Full Text Request