Retrospective And Prospective Studies On Long-term Use Of Bevacizumab

This thesis consists of two parts:the literature review and the clinical observation.The literature review consists of two parts.The first one reviewed the research progress of bevacizumab-related cardiovascular events.This part expounded mechanism and clinical application of vascular endothelial growth factor(VEGF)inhibitors bevacizumab,summarized the occurrence and mechanism of bevacizumab-related cardiovascular events based on relevant research(such as clinical trials,meta-analysis,etc.).The second one reviewed the progress of tumor angiogenesis in traditional Chinese medicine.At present,there were few researches on bevacizumab or other antiangiogenic drugs in traditional Chinese medicine,so we summarized the understanding of Chinese medicine scholars on tumor angiogenesis and treatment based on the research progress of western medicine and the records of traditional Chinese medicine.The second part includes two clinical observations.The first one is a retrospective study of cardiovascular events caused by long-term use of bevacizumab treating malignant tumors.Background:With the development of anti-tumor therapy,the survival period of tumor patients is gradually extended,at the same time,treatment related cardiovascular events are gradually manifested,affecting patient’s quality of life,and even leading to change tumor treatment or death.Bevacizumab has been widely used in clinical practice and the duration was gradually extended,so the safety of long-term bevacizumab is a concern.Objective:To explore the incidence of cardiovascular toxicity in patients with long-term use of bevacizumab in China-Japan friendship hospital.Methods:A retrospective study was conducted to investigate the patients who were treated with bevacizumab in China-Japan friendship hospital from January 1,2016 to June 30,2019.Data of patients with long-term application of bevacizumab meeting inclusion and exclusion criteria were collected,and basic patient data,cardiovascular risk factors,diagnosis and treatment,bevacizumab use,and relevant examination results(blood pressure,ECG,echocardiography,myocardial infarction,coagulation function,etc.)were sorted out.Then,we through electronic case system and telephone follow-up way obtained the happening of cardiovascular events.SPSS25.0 software was used to perform statistical analysis and calculate the incidence of cardiovascular events in patients who long-term application of bevacizumab.Results:A total of 116 patients were included in the study.After long-term treatment with bevacizumab,the incidence of hypertension was 19.8%and the incidence of severe hypertension was 3.4%,the incidence of heart failure was 0.9%,the incidence of venous thromboembolic events was 3.4%and the incidence of arterial thromboembolic events was 6.0%.Conclusion:The incidence of cardiovascular events in patients who long-term application of bevacizumab is consistent with the existing data,it provides a basis for the safety of long-term application bevacizumab.The second one is a prospective clinical observation of traditional Chinese medicine(TCM)syndromes before and after bevacizumab treatment.Background:Bevacizumab has been widely used in clinical practice,but there are few researches on bevacizumab or other anti-tumor angiogenic drugs in Chinese medicine.So the understanding of Chinese medicine is still unclear.Objective:To explore the TCM syndromes of patients before and after bevacizumab treatment.Methods:Patients were prospectively enrolled according to inclusion and exclusion criteria,basic data of patients(name,gender,age,contact information,medical record number,diagnosis),symptoms,tongue image,pulse pattern and TCM syndrome were recorded in detail,meanwhile the patients’ tongue image was photographed.The data before the initial use of bevacizumab in the enrolled patients were the baseline status,and the patients were closely followed.Symptoms,tongue image,pulse pattern and TCM syndrome were recorded.The follow-up was up to January 20,2020.All data were collected and recorded in Excel.Statistical analysis was conducted by SPSS25.0 software.Results:A total of 17 patients were included in the study,including 17 patients after 1 cycle of bevacizumab treatment and 9 patients after 2 cycles of bevacizumab treatment.(1)symptoms:before bevacizumab treatment,the symptoms of the patients were cough,sputum,shortness of breath,yellow complexion,purple and dark lips,palpitation,poor sleep,dry mouth,bitter mouth,and hoarseness.After 1 cycle of bevacizumab treatment,the symptoms of sputum,yellow complexion,poor sleep and bitter mouth were decreased,the symptoms of palpitations,bloody sputum and diarrhea were increased.After 2 cycles of bevacizumab treatment,the symptoms of cough,expectorated sputum,shortness of breath,yellow complexion,purple lips and poor sleep were decreased,the symptoms of dry mouth,bloody sputum,gingival bleeding and diarrhea were increased.(2)TCM syndromes:before and after bevacizumab treatment,the main TCM syndromes were phlegm-dampness syndrome of spleen deficiency(pixu tanshi zheng)and qi stagnation and blood stasis syndrome(qizhi xueyu zheng),after 2 cycles of bevacizumab treatment,phlegm-dampness syndrome of spleen deficiency(pixu tanshi zheng)and qi stagnation and blood stasis syndrome(qizhi xueyu zheng)were decreased,and the deficiency syndrome of kidney-yang(shenyang kuixu zheng)and internal heat syndrome of Yin deficiency(yinxu neire zheng)were increased.Conclusion:before and after bevacizumab treatment,the TCM syndromes were mainly phlegm-dampness syndrome of spleen deficiency(pixu tanshi zheng)and qi stagnation and blood stasis syndrome(qizhi xueyu zheng),but after 2 cycles of bevacizumab treatment,compared with before treatment,phlegm-dampness syndrome of spleen deficiency(pixu tanshi zheng)and qi stagnation and blood stasis syndrome(qizhi xueyu zheng)were less and the patient had bleeding symptoms(bloody sputum and gingival bleeding).After treatment blood stasis(xueyu zheng)was less than before,which may be related to the use of bevacizumab.The number of cases included in this study is small,therefore the clinical study with large sample size and long-term follow-up is needed to provide a stronger theoretical basis.