Olanzapine (5 mg) plus standard triple antiemetic therapy for the prevention of multiple-day cisplatin hemotherapy-induced nausea and vomiting: a prospective randomized controlled study.

OBJECTIVE: A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy. METHODS: Patients who received a 3-day cisplatin-based chemotherapy (25 mg/m2/d) were given either 5 mg olanzapine plus triple therapy with aprepitant, tropisetron, and dexamethasone (quadruple group) or 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant (triplet group). The primary endpoint was the complete response (CR) in the overall phase (OP) (0-120 h) between quadruple group and triplet group. The secondary endpoints were the CR in the acute phase (AP) (0-24 h) and delayed phase (DP) (25-120 h) between two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of chemotherapy-induced nausea and vomiting (CINV) on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical. CONCLUSION: It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

Evaluation of a Neurokinin-1 Antagonist in Preventing Multiple-day Cisplatin-induced Nausea and Vomiting.

OBJECTIVE: To perform a prospective non-randomized comparison of the effectiveness and safety of combined neurokinin-1 antagonist aprepitant treatment with the standard multiple-day cisplatin regimen for the prevention of cisplatin-induced nausea and vomiting (CINV). METHODS: Patients being administered 3-day cisplatin-based chemotherapy (25 mg/m2/d) who had never received aprepitant were given either the standard regimen (tropisetron and dexamethasone) or the aprepitant regimen (aprepitant plus tropisetron and dexamethasone). The primary endpoint was the complete response (CR) in the overall phase (OP, 0-120 h) between the combined aprepitant triple regimen group and the standard group. Secondary endpoints were the CR in the acute phase (AP, 0-24 h) and delay phase (DP, 25-120 h) between the two groups. The first time of vomiting was also compared by Kaplan-Meier curves. The impact of CINV on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded. RESULTS: A CR was achieved by 80.0% in the aprepitant group compared with 56.0% in the standard group during the OP (P =0.018)as well as during the DP. However, during the AP, the aprepitant and standard therapy groups achieved identical CR rates (98.0%, P =1.000). A longer time to first emesis was documented for the aprepitant group than for the standard group. No effect of CINV on quality of life as assessed by FLIE was reported by 44.7% of aprepitant therapy patients and 24.0% of standard therapy patients (P=0.035). The main aprepitant-related AEs were fatigue and constipation, but there was no significant difference between groups. CONCLUSION: Combined aprepitant therapy is recommended for the prevention of multiple-day CINV because of its improved CINV control rate and safety.