Caffeic Acid For Chinese Advanced Esophageal Cancer Progressing After Radiation And Chemotherapy And GASC1 Positive:A Phase Ⅲ,Multicentre,Double-Blind,Placebo-Controlled Randomised Trial

OBJECTIVE: Histones to methylation is involved in the invasion and metastasis of tumor cells,our team has confirmed that caffeic acid in mice as enzyme GASC1 histone demethylation inhibitors can delay the tumor growth,this study was to evaluate whether caffeic acid can prolong the survival of patients with advanced esophageal squamous carcinoma GASC1 express positive period and improve the patient’s quality of life.METHODS: From January 2017 to September 2018,preparatory work was completed,including clinical trial project applications,ethical review,and patent applications.At the same time,Shandong Dezhou De Pharmaceutical Co.,Ltd.was entrusted to issue test drugs,including caffeic acid and placebo.At the same time,we conducted a preliminary experiment,and patients who met the enrollment criteria recommended oral caffeic acid.Patients with advanced esophageal squamous cell carcinoma from a number of large-scale top three hospitals in Henan Province,including the First Affiliated Hospital of Henan University of Science and Technology,Nanyang Central Hospital,and Anyang Cancer Hospital,from October 20 to March2019,were given in order of drug number.medicine.Histopathological sections were subjected to immunohistochemistry.Before the enrollment,the patient’s blood routine,liver and kidney function,electrocardiogram,chest CT and vascular ultrasonography should be tested and reviewed regularly.The experimental group received oral caffeic acid tablets(100 mg/tablet),3 tablets/time,3 times/day,and the control group received oral placebo(100 mg/tablet),3 tablets/time,3 times/day,and finally uncovered by a third party.The primary endpoint was overall survival,and the secondary endpoint was the incidence of adverse events and quality of life before and after medication.RESULTS: From March 2017 to September 2018,the company successively obtained the approval of clinical trial,the approval of hospital ethics committee and the success of applying for patent.A total of 26 patients were enrolled from October2018 to March 2019,among which 12 patients had positive GASC1 expression,all of which were cytoplasmic expression.As of 12 March 2019,a total of 5 patients had died.At present,the longest survival time is 132 days,the shortest is 24 days,and more than half of patients have a survival time of more than 12 weeks.Since the trial has notbeen unblinded,safety evaluation can only be performed.No grade 3-4 adverse reactions occurred in the patients taking the medicine,and the 1-2 adverse reactions found so far were fatigue,vomiting,cough and esophageal pain.The quality of life assessment of 14 patients who had been treated for 8 weeks showed that the patients were in a stable state in the functional field,overall quality of life score and symptom field,and the results were not statistically significant(P > 0.05).The scores of fatigue,nausea,vomiting,diarrhea and total health status decreased,and the results were not statistically significant(P > 0.05).CONCLUSION:1.Because there is currently no unblinded,only drug safety evaluations can be performed.The adverse event rate of taking caffeic acid or placebo was low,no grade3-5 adverse event occurred,and the safety was good.2.After taking caffeic acid or placebo,the quality of life of patients with advanced esophageal squamous cell carcinoma basically stabilized,with slight improvement in fatigue,nausea,vomiting,diarrhea and overall health.