Correlation Between UGT1A1 Gene Polymorphism And Side Effects Of Irinotecan

Objective: Retrospective analysis of 134 patients who were hospitalized with the CPT-11 regimen in the oncology department of the Tian Jin Medical University General Hospital from April 2014 to November 2018,To summarize the incidence of adverse reactions in 82 patients who underwent UGT1A1 gene testing,aiming to understand the relationship between the UGT1A1 gene polymorphism and the incidence of adverse reactions after CPT-11 chemotherapy,and treatment after serious adverse reactions to guide clinical treatment.Method:Review the medical records and clinical tests,oncology case discussion PPT,telephone follow-up,etc.to collect clinical data of patients who have used CPT-11 chemotherapy and received UGT1A1 gene test for 4 years,and analyzed them from different angles.Result:1.Case data and clinical features: 82 patients had a large number of males,60(73.2%).Most patients are over 60 years old,with the maximum number being 60-70 years old.The KPS score was 80%,and the number of patients was 44(53.7%).57 patients with small cell lung cancer were treated with second-line therapy.Of the 25 patients with digestive system tumors,3 were first-line and 22 were second-line.2.Gene polymorphism distribution: 68 cases(82.9%)of 28 wild-type patients,13 cases(15.8%)of heterozygous mutations,and 1 case(1.2%)of homozygous mutations.There were 53 cases(64.6%)of 6 wild-type patients,25 cases(30.5%)of heterozygous mutants,and 4 cases of homozygous mutants(4.9%).3.Relationship between genetic polymorphism and adverse reactions: Combined with two genotypic loci analysis,the incidence of late-type diarrhea and thrombocytopenia in wild-type(TA6/6 and G/G)III-IV grades was higher than that of single-point mutants(TA6/7 and TAG/G,TA6/6 and TAG/A)and double-point mutants(TA6/7 and TAG/A,TA7/7 and TAG/G,TA6/6 and TAA/A)were significantly reduced(10.3%,15.8%,60%,P= 0.037,5.1%,10.5%,40%,p=0.046).In wild-type,singlepoint mutants and homozygous mutants,the incidence of grade III-IV overall toxicity was not statistically significant(30.8% vs 50% vs 80%,P=0.053),but showed a significant upward trend;There was no significant difference in the overall toxicity and hematological toxicity,delayed diarrhea,nausea,vomiting,and fatigue between the three groups(P>0.05).39 wild-type patients were compared with 5 patients with double-point mutation and 38 patients with single-point mutation.The incidence of grade III-IV thrombocytopenia and delayed diarrhea was significantly higher in the double-point mutation patients than in the wild type(40%).Vs 5.1%,p=0.011;60% vs 10.3%,p=0.004);the incidence of grade III-IV platelets,hemoglobin,neutropenia,and delayed diarrhea in single-point mutation patients was not significantly higher than that in wild-type patients.Difference(p=0.377,0.665,0.237,0.470).Comparing 5 patients with double-point mutations and 38 patients with single-point mutations,the incidence of grade III-IV delayed diarrhea was significantly higher in patients with double-point mutations than in single-point mutations(60% vs 15.8% p=0.022).Comparing the two different genotype sites,the incidence of grade III-IV hemoglobin reduction was significantly higher in patients with UGT1A1*28 mutation(TA6/7 or TA7/7)than in wild type(21.4% vs 4.4% p=0.026).The incidence of grade III-IV hemoglobin,neutrophils,thrombocytopenia,and delayed diarrhea in UGT1A1*6 mutations was not significantly different from that in wild-type patients(p=0.657,0.362,0.234,0.375).4.Special patient analysis: Of the 82 patients,49 patients received irinotecan chemotherapy for ?1 cycle,of which 16 patients had grade III-IV adverse reactions,and 4 patients did not appear severe after the first cycle of chemotherapy.Adverse reactions,but appeared after the second cycle,including 3 patients with KPS scores from 80 to 70 points;8 patients with serious adverse reactions,irinotecan reduced in different degrees of chemotherapy.5.The effects of different chemotherapy regimens and general clinical data of patients on serious adverse reactions: single and double drugs,age,gender,KPS scores and cancers had no significant difference in the incidence of serious adverse reactions among the three genotypes.Conclusion:1.The incidence of severe hematologic toxicity and delayed diarrhea in patients with UGT1A1 mutation is increasing,the relationship between UGT1A1 gene polymorphism and the incidence of adverse reactions after CPT-11 chemotherapy remains unclear.2.Combined detection of UGT1A1*28 and UGT1A1*6 genotypes can more accurately predict the occurrence of CPT-11 adverse reactions than a single genotype.3.In patients with homozygous mutations,the incidence of serious adverse reactions is high.When using CPT-11-containing chemotherapy,the response of patients should be closely monitored,preventive measures should be taken,and if necessary,reduced.4.After a serious adverse reaction,different degrees of CPT-11 reduction can reduce the incidence of serious adverse reactions in the next cycle of patients,the degree of reduction should be based on individualized differences in patients.5.Patients who received CPT-11 regimen chemotherapy did not have serious adverse reactions after the first cycle of chemotherapy,and still need to pay attention to and prevent serious adverse reactions in the next course of treatment,especially those patients with decreased KPS scores and more chemotherapy cycles.6.When a serious adverse reaction occurs,the clinician should actively develop a standardized treatment plan to control the patient's symptoms early and improve the patient's quality of life.