title: Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial.
abstract: BACKGROUND
  Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended in combination with other anti-emetic agents for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy in adults, but its efficacy and safety in paediatric patients are unknown. We did this phase 3 trial to examine the safety and efficacy of such treatment in children.
  
  
  METHODS
  In this final analysis of a phase 3, randomised, multicentre, double-blind study, patients aged 6 months to 17 years with a documented malignancy who were scheduled to receive either moderately or highly emetogenic chemotherapy were randomly assigned with an interactive voice response system to an age-based and weight-based blinded regimen of aprepitant (125 mg for ages 12-17 years; 3·0 mg/kg up to 125 mg for ages 6 months to <12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for ages 12-17 years; 2·0 mg/kg up to 80 mg for ages 6 months to <12 years) on days 2 and 3, or placebo plus ondansetron on day 1 followed by placebo on days 2 and 3; addition of dexamethasone was allowed. Randomisation was stratified according to patient age, planned use of chemotherapy associated with very high risk of emetogenicity, and planned use of dexamethasone as an anti-emetic. Ondansetron was dosed per the product label for paediatric use or local standard of care. The primary efficacy endpoint was the proportion of patients who achieved complete response (defined as no vomiting, no retching, and no use of rescue medication) during the 25-120 h (delayed phase) after initiation of emetogenic chemotherapy. Efficacy and safety analyses were done with all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01362530.
  
  
  RESULTS
  Between Sept 22, 2011, and Aug 16, 2013, 307 patients were randomly assigned at 49 sites in 24 countries to either the aprepitant group (155 patients) or to the control group (152 patients). Three patients in the aprepitant group and two in the control group did not receive study medication, and thus were excluded from analyses. 77 (51%) of 152 patients in the aprepitant group and 39 (26%) of 150 in the control group achieved a complete response in the delayed phase (p<0·0001). The most common grade 3-4 adverse events were febrile neutropenia (23 [15%] of 152 in the aprepitant group vs 21 [14%] of 150 in the control group), anaemia (14 [9%] vs 26 [17%]), and decreased neutrophil count (11 [7%] vs 17 [11%]). The most common serious adverse event was febrile neutropenia (23 [15%] patients in the aprepitant group vs 22 [15%] in the control group).
  
  
  CONCLUSIONS
  Addition of aprepitant to ondansetron with or without dexamethasone is effective for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients being treated with moderately or highly emetogenic chemotherapy.
  
  
  BACKGROUND
  Merck & Co., Inc.
authors.affiliation: Department of Pediatrics, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Children's Hospital, Seoul, South Korea.
authors.forename: Hyoung Jin
authors.initials: HJ
authors.lastname: Kang
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Loftus
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Arlene
authors.initials: A
authors.lastname: Taylor
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA.
authors.forename: Cara
authors.initials: C
authors.lastname: DiCristina
authors.affiliation: Merck & Co., Inc., Kenilworth, NJ, USA. Electronic address: stuart.green@merck.com.
authors.forename: Stuart
authors.initials: S
authors.lastname: Green
authors.affiliation: Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children's Hospital, Rotterdam, Netherlands.
authors.forename: Christian Michel
authors.initials: CM
authors.lastname: Zwaan
mesh_terms: D000293:Adolescent; D000328:Adult; D000077608:Aprepitant; D002648:Child; D002675:Child, Preschool; D003907:Dexamethasone / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D007223:Infant; D008297:Male; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009025:Morpholines; D000077608:Aprepitant; D003907:Dexamethasone