Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Objectives: 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. Materials and Methods: 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. Results: 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%, 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 including 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 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. Conclusions: 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.

Effect of Antiemetic Agents on Hiccups during Chemotherapy in Patients with Lung Cancer

“…Hiccups appeared within 3 days of beginning the chemotherapy, and the mean duration of hiccups was 3 days. [7]. Indeed, the present study confirmed that the use of dexamethasone play some role in the development of hiccups.…”

“…Some pharmacological agents are also known to be risk factors for hiccups [4]. In patients with lung cancer, hiccups can be associated with the anticancer drug cisplatin [5] as well as with the antiemetic agent dexamethasone [5] [6] and neurokinin-1 receptor antagonist [7]. Although hiccups will rarely put a patient's life at risk, they appear to negatively impact pa-…”

Expert Consensus on Effective Management of Chemotherapy-Induced Nausea and Vomiting: An Indian Perspective

“…Furthermore, scientific literature has provided good evidence on the effectiveness and safety of netupitant-palonosetron combination in both HEC and MEC settings (59)(60)(61)(62). The NCCN guideline recommends NK1 RA to be added to a 5-HT3/dexamethasone regimen for patients receiving MEC anticancer therapy who have additional risk factors, or previous treatment failure with the two-drug regimen.…”

Neurokinin-1 receptor antagonists: review of their role for the prevention of chemotherapy-induced nausea and vomiting in adults

“…Clinical studies have shown that oral NK 1 RAs are generally well tolerated with few additional AEs, mostly mild, when compared to 5-HT 3 RA plus dexamethasone (Table 3 [74,99,100] and Table 4 [8,72,73,81,83,95,96]). The most frequent AEs associated with oral NK 1 RAs are fatigue, hiccups, headache, and constipation [8,[72][73][74][75]81,86,87,95,96,105,106]. No significant effects on the QT interval were observed at supratherapeutic doses of NK 1 RAs [39,41,42,44,107].…”