Kang, H.J., Loftus, S., Taylor, A., DiCristina, C., Green, S., & Zwaan, C.M. (2015). Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: A randomised, double-blind, phase 3 trial. Lancet Oncology, 16, 385–394. 

To assess the efficacy and safety of oral formulations of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in pediatric patients aged six months to 17 years scheduled to be treated with moderately or highly emetogenic chemotherapy

Patients were randomly assigned (but stratified by age) to the aprepitant or control regimen and were divided into two age groups: less than 12 and 12–17 years. All patients received ondansetron. Patients over 12 received a 125 mg aprepitant capsule on day 1 and 80 mg on days 2 and 3 in the aprepitant arm. The control arm received a placebo daily plus ondansetron on day 1. Patients under 12 in the aprepitant arm received powder for suspension at 3 mg/kg on day 1 with ondansetron and 2 mg/kg of aprepitant on days 2 and 3. The control regimen again received a placebo daily plus Zofran on day 1. Investigators were able to add dexamethasone at their discretion with dose reductions of 50% based on adult pharmacokinetic data.

• N = 302  
• MEDIAN AGE = 7.5 years (range = six months to 17.8 years)
• MALES: 84 (55%) aprepitant group, 79 (53%) control group, FEMALES: 68 (45%) aprepitant group, 71 (47%) control group
• KEY DISEASE CHARACTERISTICS: Patients with a documented malignancy (original or relapse) who were scheduled to receive chemotherapy with at least a moderate risk of emesis and who were expected to receive ondansetron as part of their chemotherapy-induced nausea and vomiting (CINV) regimen
• OTHER KEY SAMPLE CHARACTERISTICS: Exclusion criteria: Vomiting 24 hours before day 1 of treatment, symptomatic primary or metastatic central nervous system malignancy causing nausea or vomiting, abdominal or pelvic external radiation therapy one week prior to treatment, use of antiemetics 48 hours before treatment, or any CYP3A4 substrates or inhibitors within seven days or inducers within 30 days of treatment

• SITE: Multi-site    
• SETTING TYPE: Not specified    
• LOCATION: Twenty-four countries

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Pediatrics

Phase 3, multicenter, randomized, double-blinded, active-comparator, controlled, parallel-group trial

• Patient diaries recorded episodes of vomiting, retching, or use of rescue medication.
• National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE v.4)
• Laboratory tests (complete blook count, chemistries, and urinalysis) and electrocardiogram

Fifty-one percent of patients in the aprepitant group achieved a complete response in the delayed phase versus 26% in the control group (p < 0.0001). The number of patients with no vomiting or rescue medication use was greater in the aprepitant group than the control group in all phases (47% versus 21% for no vomiting and 66% versus 49% for no rescue medication). The median time till the first vomiting episode was greater in the aprepitant group (96.3 hours versus 27.5 hours), and the time to first rescue medication use also was significantly longer in the aprepitant group compared to the control group. The number of patients who achieved a complete response was similar for patients aged less than 12 years receiving a powder suspension and those who received capsules. Adverse events were reported equally between groups. Serious adverse events were reported in 30% of the aprepitant group and 27% of the control group (most commonly febrile neutropenia).

A three-day age and weight adjusted oral aprepitant regimen given in combination with ondansetron with or without dexamethasone safely provided a significant benefit in preventing CINV in moderately to highly emetogenic chemotherapy in a pediatric population.

• Investigators added dexamethasone at their own discretion in a population that may have had a potential bias toward poorer outcomes and patients who may have had a greater history of emesis or more emetogenic chemotherapy.
• The study was funded by Merck and Co, Inc., who determined the study design, conduct, data collection, and analysis.

The addition of aprepitant to ondansetron with or without dexamethasone was safe and may be effective in the prevention of CINV in pediatric patients receiving moderately to highly emetogenic chemotherapy.