Herrington, J.D., Jaskiewicz, A.D., & Song, J. (2008). Randomized, placebo-controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer, 112, 2080–2087.

To evaluate the efficacy of one-day versus three-day administration of aprepitant in combination with palonosetron and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving highly emetogenic chemotherapy (HEC)

• Patients were randomization to three arms.
  • Arm A—A single dose of 0.25 mg palonosetron and 12 mg dexamethasone before receiving HEC and 3-day regimen of aprepitant.
  • Arm B—Aprepitant at 125 mg on day 1 followed by a placebo on days 2 and 3.
  • Arm C—Palonosetron at 0.25 mg 30 minutes before chemotherapy and 18 mg dexamethasone, then placebo resembling aprepitant on days 1–3.
• All patients received 8 mg dexamethasone daily on days 2–4, and all received palonosetron 30 minutes before chemotherapy and aprepitant or placebo 60 minutes before treatment.

• The sample consisted of 75 participants.
• Age: (mean age ± SD)
  • Arm A (n = 29)—59.6 years (SD = 10.7 years)
  • Arm B (n = 30)—58.3 years (SD = 10.5 years)
  • Arm C (n = 16)—56.1 years (SD = 12.6 years)
• The percentage of female patients in arm A was 69%, in arm B was 70%, and in arm C was 87.5%; the percentage of male patients in arm A was 31%, in arm B was 30%, and in arm C was 12.5%. 
• Patients' diagnoses were breast (55%), lung (13%), head and neck (19%), and other (13%).
• The median doses of chemotherapy were similar among groups except for cyclophosphamide. Median dose of cyclophosphamide in arm A was 500 mg/m², in arm B was 600 mg/m², and in arm C was 600 mg/m² (p = 0.04).
• No differences existed between groups in terms of history of motion sickness or pregnancy-induced vomiting.

The study was conducted in a single site.

All patients were in active treatment.

This was a randomized, double-blind, placebo-controlled, comparative pilot study.

• Patients defined nausea on a 100-mm visual analog scale (VAS) ranging from 0 = no nausea to 100 = worst nausea possible.
• Patients documented, via patient diaries, the number of emetic episodes, breakthrough nausea mediation, and nausea severity during the 120-hour observation period after infusion of chemotherapy.

• Initially the study had 3 arms; however, analysis displayed severe emesis with and halted arm C (n = 16).
• Those without emesis during the first 24 hours were similar between arms A and B.
• No significant differences were found in the incidence of overall nausea and severity of nausea.
• During the acute phase, complete response was similar (67% arm A and 70% arm B; p = 0.77).
• In the delayed phase, 63% arm A and 59% arm B (p = 78) had no emesis or use of breakthrough medications.
• A complete response during both phases was observed in 56% of arm A and 52% of arm B (p = 0.78).

This study suggested that a single, 125-mg dose of aprepitant provides similar effectiveness compared to the 3-day regimen. The addition of palonosetron and dexamethasone provided protection against emesis in more than 90% of patients during the 5-day study period.

• Sample size was small with fewer than 100 subjects. 
• The potential for bias was reduced by using study methods.
• No information was provided on how often patients were rating their nausea; patients may have had nausea that was not captured in diaries.

The use of aprepitant has shown to be effective in preventing acute and delayed emesis in patients who are receiving cisplatin- and anthracycline-containing therapies.