Yuan, D.M., Li, Q., Zhang, Q., Xiao, X.W., Yao, Y.W., Zhang, Y., . . . Song, Y. (2016). 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. Asian Pacific Journal of Cancer Prevention, 17, 1661–1675. 

STUDY PURPOSE: To evaluate the efficacy and safety of neurokinin-1 receptor antagonists (NK₁s) for the prevention of chemotherapy-induced nausea and vomiting (CINV) among children and adolescents

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 38 articles (32 for overall complete response [CR] analysis, 34 for acute CR analysis, 33 for delayed CR analysis, and 35 for toxicity analysis)
• TOTAL PATIENTS INCLUDED IN REVIEW = 13,923 patients (12,820 for overall, 13,561 for acute, and 13,385 for delayed; number not reported for toxicity analysis)
• SAMPLE RANGE ACROSS STUDIES: 35–1,917 patients
• KEY SAMPLE CHARACTERISTICS: The studies occurred in multiple countries with multiple types of malignancies. NK₁s were used with 5-HT₃s and dexamethasone in 30 studies. Aprepitant was used in 29 studies (NK₁s most common).

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Pediatrics, elder care

Overall: Those with NK₁ had 71% CR, and those with out NK₁ (control group) had 56% CR (p < 0.001). Subgroup analysis showed that aprepitant had significantly higher CR than the control (64% versus 51%, p < 0.001), but fosaprepitant had no difference (p = 0.311). 

Acute Phase: Those with NK₁ had 85% CR, and those without NK₁ had 79.6% CR (p < 0.001). Subgroup analysis showed that those with oral or IV NK₁ had significantly better CR (p < 0.001 for both groups) than those without NK₁, but no significant difference occurred if NK₁ was used intravenously on day 1 followed with oral NK₁ (p = 0.685). NK₁ used in combination with 5-HT₃ alone or 5-HT₃ plus dexamethasone had higher CR (p = 0.001 and < 0.001, respectively), but no difference occurred if NK₁ was used with dexamethasone alone (p = 0.274).  

Delayed Phase: Those with NK₁ had 71% CR, and those without NK₁ had 58% CR (p < 0.001). Children or Adolescents: NK₁ had increased CR in the overall phase (p < 0.001), acute phase (p = 0.012), and delayed phase (p < 0.001).

Other Outcomes: Compared to the control group, NK₁ showed less incidence of nausea (45.2% versus 45.9%, p < 0.001), less vomiting (22.6% versus 38.9%, p < 0.001), and less use of rescue drugs (23.5% versus 34.1%, p < 0.001).

Adverse Events: NK₁ did not increase the incidence of adverse events (69% versus 65%, p = 0.204), and no difference was noted among the three pediatric studies (80% versus 77%, p = 0.497).

The review confirms that the addition of NK₁ to 5-HT₃ alone or 5-HT3 plus dexamethasone is effective in achieving complete remission of chemotherapy-induced nausea and vomiting (CINV) in the acute and delayed phases with no significant increase in adverse events. The addition of NK₁ is also effective for children and adolescents in the acute and delayed phases with no significant increase in adverse events.

• No quality evaluation
• Low sample sizes
• Only three studies evaluated efficacy and safety in children and adolescents

A NK₁, specifically aprepitant, is effective in preventing CINV during the acute or delayed phases of treatment, but the medication should be administered consistently either orally or intravenously. Changing the IV route to oral is not effective.