Clinical Study Of Fosaprepitant In The Prevention Of Nausea And Vomiting Following Highly Emetogenic Chemotherapy

Objective To investigate the efficacy and tolerability of the fosaprepitant for th e control of nausea and vomiting following highly emetogenic chemotherapy c ompared with aprepitant as positive control drug in Chinese people.Methods A total of 645 patients were randomized into fosaprepitant group(fos aprepitant/placebo 150mg dl in combination with granisetron and dexamethason e)or aprepitant group(aprepitant/placebo 125mg,d1;80mg d2-d3 plus graniset ron and dexamethasone)in a 1:1 ratio.The primary endpoint was the percenta ge of patients who had a complete response(CR)over the entire treatment cour se(0?120h,OP).Secondary efficacy endpoints included the proportions of subjects who achieved CR during the acute phase and delayed phase(0?24 and 25?120 h after chemotherapy initiation,respectively),the time to the first vomiting epis ode and the frequency of vomiting per day;the time to the first rescue therapy from the chemotherapy initiation(h)and the proportion of the patients receiving rescue therapy;the proportion of the patients without significant nausea(VAS<25mm)and the proportion of the patients without nausea(VAS<5mm);the chan ge of ECOG.It was assessed by using a non-inferiority model,with a non-inferi ority margin of 10%.The difference of the CRR was compared between two gr oups with Chi-square analysis.Results Six hundred forty-five patients were randomized to the fosaprepitant group(n=328)or aprepitant group(n=317)as full analysis(FAS).Six hundred twe nty-six patients were included in the per protocol analysis(PPS).In FAS,CR rate was 89.33%in the fosaprepitant group and 92.74%in the aprepitant group in the OP.There was no significant difference between the two groups(P=0.1330).During the AP,95.73%of patients in the fosaprepitant group reported CR com pared with 95.90%in the aprepitant group(P=1.0000).During the DP,91.16%of patients in the fosaprepitant group reported CR compared with 93.38%in the aprepitant group(P=0.3065).The fosaprepitant was not inferior to theaprepita nt in the time to rescue therapy(92.73h vs,104.02h,P=0.0458)and theincidence of rescue therapy(6.40%vs.2.84%,P=0.0389).For the secondary efficacy end points of the incidence of vomiting and nausea,there was no statistica differenc e.ECOG of per day was compared between the groups and no statistical differ ence was observated.The same conclusions were also drawn from PPS analyses.Whether the cisplatin-based chemotherapy or not,the CRR of fosaprepitant grou p was not inferior to the aprepitant group.Both regimens were well tolerated.T he most common adverse event was constipation.Conclusions Fosaprepitant provided effective and well-tolerated control of CINV associated with highly emetogenic chemotherapy in Chinese patients.It offers a more convenient alternative route for the control of chemotherapy-induced nausea and vomiting.