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. Procedure. 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 0 0.15 mg/kgt.i.d. day 2; A 80 mg and D4 mg day 3; and D 4 mg day 4) or a control regimen (D 16 mg and 0 0.15 mg/kg t.i.d. day 1; D 8 mg and 0 0.15 mg/1<g 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. Conclusion. 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. Pediatr Blood Cancer 2009;52:242-247. (C) 2008 Wiley-Liss, Inc.