Rapoport, B.L., Jordan, K., Boice, J.A., Taylor, A., Brown, C., Hardwick, J.S., … Schmoll, H.J. (2010). Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: A randomized, double-blind study. Supportive Care in Cancer, 18, 423–431. 

To determine the efficacy, safety, and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) regimens and to determine if aprepitant would provide a complete response at preventing CINV in the first 5 days (120 hours) following chemotherapy

Patients naïve to moderately or highly emetogenic chemotherapy (HEC) and scheduled to receive a single dose of MEC agent, were enrolled in the study. Group one received an aprepitant triple-therapy regimen; group two received a control regimen that included a placebo 1 hour prior to chemotherapy, ondansetron (same dosing as aprepitant group), and dexamethasone on day 1, and, on days 2 and 3, placebo once daily and ondansetron twice daily (by mouth).

• The study looked at 848 participants.
• The mean age in years for patients receiving the aprepitant regimen was 57.1 (SD = 11.8 years); the mean age for patients receiving the control regimen was 55.9 (SD = 12.6 years).
• Diagnoses were 52% breast, 20% colon, 13% lung, and 4.6% ovarian.
• Chemotherapy regimens were 52% nonanthracycline/cyclophosphamide (n = 441) and 48% anthracycline/ cyclophosphamide (n = 407).
• More than two-thirds (69%) of participants were white.
• History of motion sickness was present in 5.6% of the aprepitant group and 9.8% of the control group.
• History of vomiting during pregnancy was present in 14.2% of the aprepitant group and 17.9% of the control group.

Studies were conducted at multiple sites in the United States, Mexico, Canada, Chile, Brazil, Peru, Colombia, Panama, Hong Kong, Australia, South Africa, France, Germany, Israel, and Russia.

Patients were in active treatment.

The study was a phase III, prospective, randomized, gender-stratified, double-blind trial.

Patients recorded the time and date of nausea, retching, and vomiting episodes in diaries. Nausea was assessed daily using a 100-mm horizontal visual analogue scale (VAS). If a rescue drug was used, the drug name and date and time of administration was recorded. Common Terminology of Adverse Events, version 3.0 (CTAE v 3.0) was used to assign toxicity grades to all laboratory test results and adverse events.

• The proportion of patients reporting no vomiting during the five days (0–120 hours) following initiation of chemotherapy was significantly higher in the aprepitant group (p < 0.001).
• In both the acute and delayed phases, significantly more patients in the aprepitant group reported no vomiting compared to the control group (p < 0.001).
• More patients in the aprepitant group reported a complete response in both the acute and delayed phases (p < 0.001), and time to first vomit was longer.
• No significant differences in the reporting of adverse events were found between groups.

The aprepitant regimen provided significantly more vomiting-free time. Better control with an aprepitant–containing, triple antiemetic regimen was seen for those receiving MEC (nonanthracycline and cyclophosphamide [AC] or AC).

• Results presented were for cycle one only.
• Limited generalizability is possible because the majority of the sample was female (77%) and Caucasian (69%).

Aprepitant was effective in preventing chemotherapy-associated vomiting in patients receiving a broad range of MEC and should be considered as part of a standard antiemetic regimen.