Dongmei Yuan¹, Qin Zhang², Xinwu Xiao¹, Yanwen Yao¹, Yan Zhang¹, Yan-ling Lv³, Qian Li¹, Hong-bin Liu¹, Tangfeng Lv¹, Yong Song⁴

¹Department of Respiratory Medicine, Nanjing University School of Medicine,China Jinling Hospital, Nanjing.

²Departmentof Gynecology, Nanjing University School of Medicine, China Jinling Hospital,Nanjing.

³Departmentof Respiratory, Southeast University, China the Second Affiliated Hospital, Medicine,Nanjing.

⁴Departmentof Respiratory, China Nanjing University School of Medicine, Nanjing.

Objective：Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)?Researchers differ on this question. A systematic review and meta-analysis was performed to elucidate this issue. Method: The electronic databases were searched for randomized controlled trials that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary efficacy end point was complete response (CR: no emesis, no rescuemedication) in the acute (0-24h after chemotherapy), delayed (25-120h), and overall (0-120h) phase after chemotherapy. Sub group analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK-RAs, and age of patients included in the studies.Other outcomes of interest included the incidence of nausea, vomiting, and need of rescue therapy during the overall phase. The incidences of different typesof adverse events were also extracted to estimate the safety of NK1-RAs. Oddsratios (ORs) and 95% confidence intervals (CIs) were calculated using arandom-effects model. Result: 38RCT sinvolving 13923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs. 56.0%, P<0.001), acute phase (85.1% vs.79.6%,P<0.001), and delayed phase (71.4% vs.58.2%, P<0.001). There were three studies included patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase：OR=2.807, P<0.001; acute phase: OR=2.863, P=0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs.45.9%, P<0.001; occurrence of vomiting: 22.6%vs. 38.9%, P<0.001; usage of rescue drugs: 23.5%vs. 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports. And the toxicity rate of patients less than eighteen years old wasalso not different between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently to be detected in the patients receiving NK1-RAs. Conclusion: NK1-RAs improved the CR rate of CINV during the overall, acute, and delayed phase. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, and decrease the possibility of constipation and insomnia.

Keywords：systematic review