Low Dose Olanzapine in the Prevention Carboplatin Induced Nausea and Vomiting: a Prospective Randomized Controlled Trial

Abstract Objective To perform a prospective randomized comparison of the efficacy and safety of low-dose 5mg olanzapine（OLZ） in preventing nausea and vomiting induced by carboplatin chemotherapy.Methods All patients with malignant tumors (n=113) who received carboplatin（AUC≥5）chemotherapy were randomly divided into two groups:triplet regimen group (n=56) and standard group (n=57). The patients in the olanzapine group received 5mg olanzapine combined with 5-HT3RA and dexamethasone(DXM) triplet antiemetic regimen, whereas those in the standard group received 5-HT3RA and DXM. The primary end-points of the study were the TC(total contral) during the OP(Overall phase, 0-120h), AP(acute phase, 0-24h) and DP(delayed phase, 25-120h) phase between combined 5mg olanzapine triplet regimen group and standard group. The secondary end-points were the TP (total protection) and CR (complete response) during OP, AP and DP phase between two groups. The first time to vomiting comparion between two groups was depicted 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). Olanzapine related side-effection was also recorded.Results: (1) The primary end-point TC rate were favorable 5mg olanzapine group than standard group during the OP 62.50% (35/56) vs 31.57% (18/57) P=0.001), AP 87.50% (49/56) vs 63.15% (36/57) P=0.003 and DP 64.28% (36/56) vs 33.33% (19/57) P=0.001 respectively. (2)The secondry end-points TP were 82.14% (46/56) vs 63.15%(36/57)(P=0.024),83.92%(47/56) vs 63.15%(36/57) (P=0.012) during the OP and DP but not get statistical significance during AP between two groups respectively.The CR rate does not get statistical significance between two groups during the three periods respectively, P>0.05;(3) It was observed longer time to first emesis in the olanzapine group than standard group from Kaplan-Meier curves.The no effection on life-quality (score≥108) assessed by FILE was 62.50% vs 43.48% between two groups, P<0.05. The most common olanzapine-related side-effection is somnolence and weakness.Conclusion: The 5mg olanzapine based triplet antiemetic regimen is effective and safety in the prevention carboplatin induced nausea and vomiting especially in the control of the nausea. Name of the registry: ChiCTR2000040566Trial registration number: ChiCTR2000040566Date of registration(retrospectively registered): 2th-12-2020URL of trial registry record:https://www.chictr.org.cn/listbycreater.aspx