Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebo-controlled study of efficacy and tolerability.
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.
Gore
Lia
L
Division of Pediatric Hematology/Oncology/Bone Marrow Transplant, Children's Hospital and The University of Colorado Denver, Aurora, Colorado, USA. lia.gore@ucdenver.edu
Chawla
Sant
S
Petrilli
Antonio
A
Hemenway
Molly
M
Schissel
Debra
D
Chua
Vickey
V
Carides
Alexandra D
AD
Taylor
Arlene
A
Devandry
Suzanne
S
Valentine
Jack
J
Evans
Judith K
JK
Oxenius
Bettina
B
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
D000970:Antineoplastic Agents; D009025:Morpholines; D010919:Placebos; D000077608:Aprepitant; D017294:Ondansetron; D003907:Dexamethasone