Abstract
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. Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. A total of 38 RCTs involving 13,923 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%, <0.001), acute phase (85.1% vs 79.6%, <0.001), and delayed phase (71.4% vs 58.2%, <0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, <0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, <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%, <0.001; occurrence of vomiting: 22.6% vs 38.9%, <0.001; usage of rescue drugs: 23.5% vs 34.1%, <0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff 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 detected in patients receiving NK1-RAs. NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.
Highlights
Chemotherapy-induced nausea and vomiting (CINV) has a significant adverse effect on health-related quality of life and even has negative impacts on the continuation of chemotherapy(Martin et al, 2003a; Martin et al, 2003b)
Navari et al firstly demonstrated that neurokinin-1 receptor antagonists (NK1-RAs) improve chemotherapy-induced nausea and vomiting (CINV) when used in patients receiving cisplatin-based chemotherapy (Navari et al, 1999)
After screening of title and abstract, 95 studies that potentially met the inclusion criteria were closely scrutinized. 57 articles were further excluded for the following reasons: (i) 5 studies was not randomized control trials (RCTs); (ii) 22 articles were removed because of duplication; (iii) 13 studies were about drug interaction; (iv)2 articles were economic analyses of aprepitant-containing regimens; (v) 15 studies were about the application of NK1-RAs in diseases other than CINV
Summary
Chemotherapy-induced nausea and vomiting (CINV) has a significant adverse effect on health-related quality of life and even has negative impacts on the continuation of chemotherapy(Martin et al, 2003a; Martin et al, 2003b). Recent studies and guidelines recommend that the addition of NK1-RAs to the 5-HT3RAs plus corticosteroid combination as the most effective regimen for controlling both acute and delayed CINV (Aapro et al, 2015). Dos Santos LV et al demonstrated that NK1-RAs increased CINV control in the acute, delayed, and overall phase, and NK1-RAs are effective for both HEC and MEC. Roila F found that in cancer patients submitted to cisplatin-based chemotherapy, aprepitant plus dexamethasone was not superior to metoclopramide plus dexamethasone in preventing delayed emesis (complete response rate was 80.3% and 82.5%, respectively) (Roila et al, 2015). The aim of this study is to provide an updated systematic review of the efficacy and safety of NK1-RAs in the prevention of CINV, and to evaluate the use of NK1-RAs in pediatric and adolescent patients
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