The Associantion Of Related Gene Polymorphisms With The Efficacy Of Cisplatin Multiday Chemotherapy-induced Nausea And Vomiting

Objective It is a research hotspot to achieve individualized and efficient management for accurate prevention of CINV（Chemotherapy-induced nausea and vomiting）by discussing the differences of gene polymorphism among individuals.As neurokinin 1 receptor antagonists and olanzapine play a more and more important role in the prevention and treatment of CINV,it is planned to conduct a prospective randomized controlled clinical trial of olanzapine or aprepitant in the prevention and treatment of CINV.During this period,we mainly studied the relationship between the polymorphisms of ABCB1 rs1045642,rs2032582,rs1128503,GTF2E1 rs447978,DRD2 rs6277,rs1076560,COMT rs4680 and prevention and treatment of nausea and vomiting induced by cisplatin multi-day chemotherapy.Methods 210 patients were enrolled in this study,and 10 ml of peripheral blood was collected from 90 different patients before chemotherapy.Patients who received cisplatin multi-day chemotherapy were prospectively randomly divided into two groups:olanzapine combined with 5-HT₃RA（5-serotonin-3 receptor antagonists）,dexamethasone or aprepitant combined with 5-HT₃RA and dexamethasone.The indicators for comparing and evaluating the antiemetic efficacy of the two groups of patients were as follows.The main evaluation index were total protection of overall phase（0-120h）,acute phase（0-24h）and delay phase（24-120h）.The secondary index were the complete response and total control of overall phase,acute and delay phase.Kaplan-Meier curve was used to compare the time when the first vomiting occurred in the two groups.FLIE scale evaluated the effect of CINV on the quality of life of patients,evaluated the related adverse reactions of olanzapine and aprepitant,and compared the economic cost of antiemetic drugs per cycle between the two groups.DNA samples of patients were genotyped by single nucleotide polymorphism,and the correlation between genotype and prophylactic antiemetic efficacy was analyzed.Results（1）The TP rate of olanzapine group was slightly better than the aprepitant group in total phase 54.81%（57/47）VS 54.72%（58/48）（P=0.989）.And the TP rate of acute phase and delay phase were 94.23%（98/6）VS 95.45%（98/8）（P=0.606）,54.81%（57/47）VS 54.72%（58/48）（P=0.989）respectively.（2）There was no significant difference in the rates of CR and TC between olanzapine and aprepitant groups in overall phase,acute phase and delayed stage（P>0.05）.（3）FLIE scale score greater than 108 indicated that CINV had no effect on patients’quality of life,and there was no statistical difference between the two groups in this study（P=0.960）.（4）The first vomiting occurred later in aprepitant group than that in olanzapine group（P=0.564）;（5）The related adverse reaction of olanzapine was mainly the somnolence,and of aprepitant was mainly the constipation.（6）The economic effect of olanzapine group was better than that of aprepitant group.（7）Univariateχ²test showed that delayed TP was associated with ABCB1 rs1045642 CC+CT genotypes in olanzapine group and ABCB1 rs2032582 non-GG genotypic locus in aprepitant group,and no significant correlation was found in other genotypes.（8）Multivariate Logistic regression analysis showed that the gender（P=0.000）and rs1045642 genotypes（P=0.002）were independent prognostic factors of delayed phase of CINV.Conclusion The efficacy of olanzapine triple antiemetic regimen in preventing CINV and improving the quality of life induced by cisplatin is similar to that of aprepitant triple antiemetic regimen.The side effects of olanzapine triple antiemetic regimen are less and the cost-benefit ratio is high,which is beneficial to clinical promotion.The delayed CINV total protection rate was increased in male patients and ABCB1 rs1045642CC+CT genotype carriers which can be used as potential clinical predictors to predict the protective effect of CINV.