| Objective: Cisplatin multi-day chemotherapy is commonly used in clinical practice,but CINV control is still unsatisfactory in multi-day chemotherapy,especially delayed phase response.With NK-1 receptor inhibitors(NK-1 RA)and olanzapine play an increasingly important role in CINV prevention and treatment,in order to achieve individualized and efficient management of CINV.We aimed to compare the efficacy and safety of fosaprepitant plus triple therapy(5 mg olanzapine,palonosetron and dexamethasone)versus triple therapy alone in preventing chemotherapy-induced nausea and vomiting(CINV)in patients receiving multi-day cisplatin-based treatment.We also aimed to compare the routine regimen(fosaprepitant and/or olanzapine administered on day 1)and delayed regimen(fosaprepitant and/or olanzapine delayed for 1 day)in preventing CINV.Methods: In this prospective randomized controlled trial,patients receiving cisplatin-based three-day chemotherapy(25 mg/m2/day)received fosaprepitant plus triple therapy(5 mg olanzapine,palonosetron,and dexamethasone)or triple therapy alone,and received conventional and delayed regimens in quadruple therapy and triple therapy,respectively.The primary endpoint was the total protection rate(TP)in the overall phase(OP,0-120 h).TP was defined as no vomiting or severe retching requiring rescue measures and a maximum nausea score of ≤ 25 mm on a 100 mm scale.The secondary endpoints were the TP rates during the acute phase(AP,0-24 h)and delayed phase(DP,25-120 h)and the complete response(CR)and total control(TC)rates during AP,DP,and OP.Kaplan-Meier curves were used to compare the time to the first vomiting between treatments.The Functional Living Index-Emesis(FLIE)questionnaire was used to assess the impact of CINV on patients quality of life and the antiemetic drug-related adverse events(AEs).Results:(1)Fosaprepitant plus triple therapy achieved a higher TP rate during OP than triple therapy alone 56.9%(58/102)vs.40.4%(42/104)(P = 0.018).(2)Fosaprepitant plus triple therapy also produced a higher TP rate than triple therapy alone during DP 57.8%(59/102)vs.40.4%(42/104)(P = 0.012)but not during AP 88.2%(90/102)vs.86.5%(90/104)(P = 0.714).(3)In addition,fosaprepitant plus triple therapy achieved higher CR rates than triple therapy alone during DP 86.3%(88/102)vs.71.2%(74/104)(P = 0.008)and OP 83.3%(85/102)vs.70.2%(73/104)(P = 0.026),but not during AP 93.1%(95/102)vs.92.3%(96/104)(P =0.819).(4)There were no statistically significant differences in the TC rate during AP,DP,or OP between the two antiemetic combinations.(5)The delayed regimen appeared to be more effective than the routine regimen in terms of the primary and secondary endpoints,but the differences were not statistically significant.(6)The Kaplan-Meier curves showed that fosaprepitant plus triple therapy delayed the first vomiting relative to triple therapy alone(P =0.000).(7)The self-reported FLIE scores revealed no differences in daily life quality between the two treatment.(8)Common antiemetics-related AEs in both groups were almost identical and included fatigue,somnolence,constipation,hiccup,loss of appetite,dizziness,abdominal distension,and headache.Conclusions: Fosaprepitant plus triple therapy(5 mg olanzapine,palonosetron and dexamethasone)demonstrated superiority over triple therapy alone for CINV control in patients receiving multiple-day cisplatin-based treatment.The quadruple antiemetic regimen may serve as an alternative therapy for preventing CINV induced by multiple-day cisplatin-based chemotherapy. |
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