Cardiotoxicity Of Fluorouracil In Patients With Digestive Tract Tumors:A Systematic Review And Meta-analysis

Background: Although advanced diagnosis and treatment technologies have significantly reduced tumor-related mortality,the incidence and mortality of treatmentrelated cardiotoxicity are increasing day by day,seriously affecting the survival and prognosis of cancer patients.Fluorouracil are antimetabolites widely used in malignant tumors such as the digestive tract,and are the second largest class of drugs that cause cardiotoxicity.However,people often ignore or lack awareness of their cardiotoxicity and their hazards.This article aims to accurately assess the incidence,clinical characteristics,and risk factors of fluorouracil-related cardiotoxicity in patients with gastrointestinal tumors.Methods: The databases of PubMed,Embase,Web of science and Cochrane Library were searched by computer to search for clinical studies on fluorouracil drugs in the treatment of digestive tract or gastrointestinal tumors induced cardiotoxicity,and a systematic review and meta-analysis were conducted.Results: The proportion of cardiotoxicity in 8976 patients of 29 studies was 4.28%,95%CI: 2.81-6.48,p<0.001),and the cardiotoxicity-related mortality was 0.39%(95%CI: 0.16-0.97,p<0.001),The proportion of serious cardiac adverse events was 0.45%(95% CI: 0.19-1.06,p<0.001).The most common symptom of cardiotoxicity is chest pain,with an incidence rate of about 2.27%(95% CI: 1.56-3.29,p<0.001).Other common symptoms include dyspnea(0.89%),palpitations(0.64%),hypertension(0.04%),heart failure(0.39%).The incidence of cardiotoxicity in the 5-FU group was 4.00%,which was significantly higher than that in the capecitabine group(3.63%,p<0.001).The abnormal rate of ECG was 2.49%(95%CI: 1.68-3.66,p<0.001),2.54% of patients had arrhythmia,and 1.73% of patients had ischemic changes.Previous ischemic heart disease(RR: 3.13,95% CI: 2.00-4.91,p<0.001),continuous intravenous infusion of 5-FU,combined therapy regimen,especially in combination with platinum drugs may be associated with cardiotoxicity risk.The type of study,study sample size,and definition of cardiotoxicity may affect the proportion of cardiotoxicity.Conclusion: For patients with gastrointestinal cancer,the proportion of fluorouracilrelated cardiotoxicity is about 4.28%,and the mortality rate associated with it is about 0.39%.The most common clinical symptom is chest pain,and myocardial ischemia and arrhythmia are the most common ECG changes.Basic ischemic heart disease,continuous intravenous infusion of 5-FU,combined therapy regimen,especially in combination with platinum drugs may be susceptible factors for cardiotoxicity.