Retrospective Analysis Of Severe Adverse Reactions Caused By Oxaliplatin Combined With Fluorouracil In Patients With Gastrointestinal Malignancies

OBJECTIVE: The safety of oxaliplatin combined with fluorouracil in the treatment of gastrointestinal malignant tumors was retrospectively analyzed.To explore the correlation between neurotoxicity,allergic reaction,hand-foot syndrome and previous disease history,previous allergy history,pathological stage and number of chemotherapy cycles;To explore the correlation between DPYD,MTHFR,GSTP1,XRCC1 gene polymorphisms and adverse reactions to chemotherapy in patients with gastrointestinal malignant tumor.METHODS: The data of patients with gastrointestinal malignant tumor who received oxaliplatin combined with fluorouracil on February 21,2014 and December29,2020 in the Department of Oncology of the First Affiliated Hospital of China Medical University were retrospectively collected.The patients’ gender,age,previous disease history,previous allergy history,pathological stage,medication cycle number,medication dose,and adverse reactions after medication were collected.The clinicopathological data and genetic test results(DPYD,MTHFR,GSTP1,XRCC1)of patients with gastrointestinal malignant tumor were collected.The correlation between neurotoxicity,allergic reaction and hand-hand syndrome caused by oxaliplatin combined with fluorouracil in patients with gastrointestinal malignant tumor and previous disease history,previous allergy history,pathological stage and number of chemotherapy cycles was analyzed,and the correlation between gene polymorphism and adverse reactions of chemotherapy in patients with gastrointestinal malignant tumor was analyzed.Results: A total of 1046 patients receiving oxaliplatin combined with fluorouracil in the treatment of gastrointestinal malignancies were enrolled.Fluorouracil oxaliplatin into classes of adverse reactions caused by drug treatment of patients with gastrointestinal malignant tumor mainly for neurotoxicity,hematology toxicity and gastrointestinal tract toxicity,mostly I-class II,III and IV level the brotherhood of high incidence of adverse reactions of syndrome(7.27%),nerve toxicity(6.60%),diarrhea(5.07%),and three kinds of chemotherapy regimens in extremities syndrome has significant correlation(P = 0.037).The occurrence of neurotoxicity and anaphylaxis in patients was not related to the history of diabetes,but was related to the number of chemotherapy cycles.The higher the number of chemotherapy cycles,the higher the incidence of neurotoxicity and allergic reactions.The median number of cycles of neurotoxicity in patients treated with oxaliplatin was 6,the median cumulative dose was 590mg/m2,the incidence of neurotoxicity was 48.28%,and the incidence of grade III-IV neurotoxicity was 6.60%.The median number of cycles of anaphylaxis to oxaliplatin was 6,and the median cumulative dose was 810mg/m2.The incidence of allergic reaction was 4.68%,and the incidence of grade III-IV allergic reaction was1.72%.The higher the number of chemotherapy cycles,the higher the incidence of hand-foot syndrome.The incidence of hand-foot syndrome was 44.74%,and the incidence of severe hand-foot syndrome was 7.27%.The incidence of nausea of DPYD-rs1801159 mutant was higher than that of wild type.The incidence of diarrhea of MTHFR-rs1801133 mutant was higher than that of wild type.The incidence of neutropenia and neurotoxicity in the wild type of GSTP1-rs1695 was higher than that in the mutant type.The wild type of XRCC1-rs25487 has a higher incidence of constipation than the mutant type.Conclusion: The adverse reactions caused by oxaliplatin combined with fluorouracil in the treatment of patients with gastrointestinal malignant tumor,such as neurotoxicity,allergic reaction and hand-foot syndrome,are correlated with the number of chemotherapy cycles.The more cycles of chemotherapy patients receive,the higher the incidence of neurotoxicity,allergic reaction and hand-foot syndrome.DPYD,MTHFR,GSTP1 and XRCC1 gene polymorphisms can predict the adverse reactions of patients with gastrointestinal malignant tumor during chemotherapy.For high-risk patients prone to adverse reactions during chemotherapy,strict follow-up plan should be developed to closely monitor the occurrence of adverse reactions in patients and timely adjust the treatment plan.