Clinical Study Of Comparison Of Metoclopramide And Aprepitant To Prevent Delayed Chemotherapy-induced Nausea And Vomiting

BackgroundChemotherapy-induced nausea and vomiting(CINV)is the most unpleasant and distressing side effects of chemotherapy.The 5-HT3 receptor antagonists,NK1 receptor antagonist and dexamethasone are effective agents for the prevention of CINV.However,the price of NK-1 receptor antagonist aprepitant is relatively high,and there are still about 25%to 35%of patients receiving HEC after the use of aprepitant in the delayed phase(24 to 120 hours after chemotherapy)CINV failed to get effective response.Therefore,looking for other effective drugs to prevent delayed CINV is currently an important clinical problem.A recent clinical study by Rolia et al showed that methamphetamine combined with dexamethasone was not inferior to aprepitant combined with dexamethasone(complete remission rate,82.5%vs 80.3%,P>0.05).This study has given new options for delayed CINV,but there are two shortcomings:Firstly,this study used aprepitant in the acute phase(chemotherapy after 0～24h)that may affect the role of follow-up metoclopramide in the delayed phase CINV;Secondly,the daily dose of metoclopramide is 80mg in this study,and Chinese antiemetic guideline recommended daily use of metoclopramide is 10-40mg.Chinese human body surface area is smaller than the European,Whether metoclopramide daily dose of 40mg can effective control of delayed vomiting remains to be further confirmed by clinical studies.ObjectiveTo compare the effectiveness and safety of metoclopramide and apprepitant when combined with dexamethasone for prophylaxis of delayed chemotherapy-induced nausea and vomiting(CINV)in patients with highly emetogenic chemotherapy(HEC).In the meanwhile,to compare compare the effectiveness and safety of two generation of 5HT3 receptor antagonists both combined apprepitant and dexamethasone for prevention of CINV in patients with HEC.MethodsPatients with a malignant solid tumor who would receive HEC were randomly assigned to one of four group.MPD group received a combination of metoclopramide(20mg bid d2-4),palonosetron(0.25mg dl)and dexamethasone(20mg d1,8mg bid d2-4),and APD group received aprepitant(125mg d1,80mg d2-3),palonosetron(0.25mg dl)and dexamethasone(12mg d1,8mg qd d2-4),and ATD group received aprepitant(125mg dl,80mg d2-3),tropisetron(0.5mg dl)and dexamethasone(12mg dl,8mg qd d2-4)for emesis control,and PD group received a combination of palonosetron(0.25mg d1)and dexamethasone(20mg d1,8mg bid d2-4)for emesis control.The primary end point was complete response(defined as no vomiting and no rescue medication,CR)at the delayed period(24-120h after the start of chemotherapy)and secondary end point was the complete control(defined as no vomiting,no rescue medication and no more than sever nausea),no nausea and the incidence of side-effects.ResultsFrom July 2015 to January 2017,a total of 123 patients were included,and 122 patients were evaluable.1.The CR rate of MPD group,APD group and PD group in the delay period Was 87.1%,81.3%and 71.9%respectively,the difference was not statistic significant(P>0.05).For the control of nausea,the complete control rate of the APD group was 78.1%,followed by MPD group(74.2%),and finally PD group(68.8%),the difference was not statistic significant(P>0.05).The incidence of no nausea in MPD group,APD group and PD group was 48.4%,46.9%and 46.9%,respectively,the difference was not statistically significant(P>0.05).2.The CR rate of APD group group and ATD group in overall period were 81.3%and 77.4%,respectively,the difference was not statistic significant(P>0.05),and the CR rate in acute period and delayed period were 96.9%vs 93.5%、81.3%vs 77.4%,respectively,the difference was not statistic significant.For the control of nausea,the complete control rate and no nausea of the APD group and the ATD group were 78.1%vs 74.2%(P>0.05),46.9%vs 41.9%(P>0.05),respectively,both difference were not statistic significant.3.The most common adverse events were constipation,fatigue and hiccups,and all adverse reactions were tolerable.No significant difference were found in side effects(P>0.05),all the patient can tolerate.ConclusionThe triple antiemetic therapy with metoclopramide,palonosetron,and dexamethasone showed similar efficacy and safety with the standard triple antiemetic therapy of aprepitant,palonosetron,and dexamethasone in HEC.The triple antiemetic prophylaxis contain palonosetron was similar to triple antiemetic prophylaxis contain tropisetron.