Aprepitant in adolescent patients for prevention of chemotherapy‐induced nausea and vomiting: A randomized, double‐blind, placebo‐controlled study of efficacy and tolerability

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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. 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 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 AUC0–24 hr and Cmax 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.