title: Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability.
abstract: BACKGROUND
  The neurokinin-1 receptor antagonist aprepitant, plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents.
  
  
  METHODS
  Patients age 11-19 years old receiving emetogenic chemotherapy were randomized 2:1 to aprepitant triple therapy (aprepitant [A] 125 mg p.o., dexamethasone [D] 8 mg p.o., and ondansetron [O] 0.15 mg/kg i.v. t.i.d. day 1; A 80 mg, D 4 mg, and O 0.15 mg/kg t.i.d. day 2; A 80 mg and D 4 mg day 3; and D 4 mg day 4) or a control regimen (D 16 mg and O 0.15 mg/kg t.i.d. day 1; D 8 mg and O 0.15 mg/kg t.i.d. day 2; and D 8 mg days 3 and 4). The primary endpoint was the difference in drug-related adverse events during and for 14 days following treatment. Efficacy and aprepitant pharmacokinetics were assessed.
  
  
  RESULTS
  Baseline characteristics were similar between aprepitant (N = 28) and control (N = 18) groups. Febrile neutropenia was more frequent in the aprepitant group (25% vs. 11.1%). Complete response (CR) rates were 35.7% for aprepitant triple therapy versus 5.6% for the control group. Mean plasma aprepitant AUC(0-24 hr) and C(max) on day 1 and mean trough concentrations on days 2 and 3 were consistently lower compared to historical data obtained from healthy adults; however, the differences were not clinically significant.
  
  
  CONCLUSIONS
  Aprepitant triple therapy was generally well tolerated; CR were greater with aprepitant, although not statistically significant. Pharmacokinetics suggest that the adult dosing regimen is appropriate for adolescents.
authors.affiliation: Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Children's Hospital and The University of Colorado Denver, Aurora, Colorado, USA. lia.gore@ucdenver.edu
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.forename: Sant
authors.initials: S
authors.lastname: Chawla
authors.forename: Antonio
authors.initials: A
authors.lastname: Petrilli
authors.forename: Molly
authors.initials: M
authors.lastname: Hemenway
authors.forename: Debra
authors.initials: D
authors.lastname: Schissel
authors.forename: Vickey
authors.initials: V
authors.lastname: Chua
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Carides
authors.forename: Arlene
authors.initials: A
authors.lastname: Taylor
authors.forename: Suzanne
authors.initials: S
authors.lastname: Devandry
authors.forename: Jack
authors.initials: J
authors.lastname: Valentine
authors.forename: Judith K
authors.initials: JK
authors.lastname: Evans
authors.forename: Bettina
authors.initials: B
authors.lastname: Oxenius
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077608:Aprepitant; D019540:Area Under Curve; D002648:Child; D003907:Dexamethasone / Q000008:administration & dosage; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008657:Metabolic Clearance Rate; D009025:Morpholines / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009503:Neutropenia / Q000139:chemically induced; D017294:Ondansetron / Q000008:administration & dosage; D010919:Placebos; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D010919:Placebos; D000077608:Aprepitant; D017294:Ondansetron; D003907:Dexamethasone