Gore, L., Chawla, S., Petrilli, A., Hemenway, M., Schissel, D., Chua, V., … Adolescent Aprepitant in Cancer Study Group. (2009). Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: A randomized, double-blind, placebo-controlled study of efficacy and tolerability. Pediatric Blood and Cancer, 52, 242–247.

To evaluate the tolerability, efficacy, and pharmacokinetics of aprepitant with a 5-HT₃ receptor antagonist and corticosteroid in adolescents with cancer

Patients were randomized to receive either a regimen of aprepitant plus dexamethasone and ondansetron or the control arm of ondansetron and dexamethasone. On the day of chemotherapy, aprepitant or placebo was administered 1 hour before and dexamethasone and ondansetron were given 30 minutes before chemotherapy. Rescue medication was permitted. Patient follow-up was done between days 6 and 8 and between days 19 and 29. Patients recorded episodes of vomiting in diaries for five days following chemotherapy. For the experimental arm, aprepitant was given at 125 mg day 1, 80 mg days 2 and 3, 4 mg day 4; 8 mg dexamethasone day 1, 4 mg days 2 and 3; and ondansetron at 0.15 mg/kg, three times per day on days 1 and 2. In the control arm, patients received 16 mg dexamethasone on day 1, 8 mg on days 2–4, and ondansetron at 0.15 mg/kg, three times per day on days 1 and 2.

• The study consisted of 40 participants.
• The mean age was 15 years old, with a range of 11–19 years.
• The sample was 29% female and 61% male.
• The most common diagnosis was bone sarcoma.
• Patients were scheduled to receive emetogenic chemotherapy or had previously intolerable therapy because of chemotherapy-induced nausea and vomiting (CINV).

The study was conducted at a single outpatient setting at Children’s Hospital, University of Colorado.

The patients were pediatric, in active treatment.

This was a randomized, double-blind, parallel group study.

• Complete response (CR) was defined as no episodes of vomiting and no use of rescue medication.
• Measurement instruments were patient diaries and Common Terminology for Adverse Events (CTAE).

• No serious, drug-related, adverse events were reported. Among those treated with aprepitant, the most common reported side effect was hiccups (15.6%).
• Comparison of response rates were, overall, 28.6% with aprepitant and 5.6% with controls.
• In the acute phase (0–24 hours), 60.7% with aprepitant had CR, compared to 38.9% in controls.
• In the delayed phase (24–120 hours), 35.7% with aprepitant had CR, compared to 5.6% in the control group.
• Analysis showed that the treatment difference in favor of the aprepitant triple therapy began at about 15 hours after chemotherapy administration.
• Pharmacokinetic analysis was compared to that previously done in adults and showed more variability in adolescents.

More patients in the aprepitant group achieved CR for CINV control in the acute and delayed phases, as well as in the overall study period. The addition of aprepitant to the antiemetic regimen appeared to be well tolerated in adolescents, with an overall adverse event profile similar to that seen in adults.

• The study had a small sample of less than 100 participants.
• The study was likely underpowered to demonstrate statistically significant results.
• The chemotherapeutic regimens were not described, so the emetogenicity was not clear and cannot be compared to other groups.
• The study was for a short period of only five days.
• The measure of CR was apparently based on patient diary results. Description of actual vomiting episodes was not provided, and compliance with diary recording was not described, although this is a method that is well known to be potentially problematic.
• Efficacy in terms of nausea was not discussed, as CR was defined only in terms of actual vomiting and use of rescue medication. No additional objective measure of the severity of nausea or vomiting was included.
• Statistical significance was not reported; only confidence intervals for findings were given.

Findings suggest that aprepitant in addition to standard antiemetic treatment is tolerable and may be helpful in patients between the ages of 11 and 19. Further study of the efficacy of antiemetic regimens in the pediatric and adolescent populations is warranted.