Saito, H., Yoshizawa, H., Yoshimori, K., Katakami, N., Katsumata, N., Kawahara, M., & Eguchi, K. (2013). Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: A multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Annals of Oncology, 24, 1067–1073.

To evaluate the efficacy and safety of single-dose fosaprepitant in combination with IV granisetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC) containing cisplatin at 70 mg/m² or higher

Patients receiving high-dose cisplatin were randomized to one of two groups (fosaprepitant or placebo). On day 1, one hour before antineoplastic treatment, both groups received IV granisetron 40 µg/kg and an IV infusion over 20-30 minutes of either fosaprepitant 150 mg or placebo. Dexamethasone also was given on day 1 (10 mg given to the fosaprepitant group and 20 mg given to the placebo group). Aprepitant is known to increase plasma dexamethasone concentrations when used in combination with dexamethasone; therefore, to achieve comparable plasma levels of dexamethasone, the fosaprepitant group received a half dose of dexamethasone on days 1 and 2 only. On day 2, both groups received dexamethasone 4 mg and 8 mg, respectively. On day 3, both groups received dexamethasone 8 mg IV, administered in the morning.

• The study consisted of 340 participants.
• Participants' ages ranged from 25-86.
• The majority of patients were male (74%), and 26% were female.
• Diagnoses were respiratory (71%), genitourinary (10%), digestive (8%), head and neck (7%), and other (4%).
• In the standard (placebo) group, 64% of the participants did not consume alcohol whereas, in the fosaprepitant group, 50% had no alcohol intake.
   

This was a multisite study conducted at 68 institutions in Japan.

All patients were in active antitumor treatment.

This was a multicenter, placebo-controlled, double-blind, randomized, parallel study.

Patients kept self-assessment symptom diaries. Vomiting was defined as one episode of emesis or retching; nausea was assessed on most intense during a 24 hour-period of time.

• The percentage of patients who achieved a complete response (CR) in the overall phase (1-120 hours) was significantly higher in the fosaprepitant group than in the control group (64%, 95% confidence interval [CI] 16%-46%) versus 47% (95% CI, 10%-36%, p = 0.0015).
• CR rates in the acute and delayed phases were significantly higher in the fosaprepitant group than in the control group (acute phase: 94% versus 81%, P = 0.0006; delayed phase: 65% versus 49%, p  = 0.0025).
• Although the prevalence of a CR was decreased in the delayed phase, the difference between the two groups was higher in the delayed phase than in the acute phase (16% versus 13%).
• In patients who had received cisplatin and experienced vomiting, CR rates in the overall phase were higher in the fosaprepitant group than in the control group (60% versus 30.3%).
• Significant nausea in all phases and percentages of those with no rescue therapy in the overall phase did not differ significantly.

A single-dose administration of fosaprepitant (150 mg), used in combination with granisetron and dexamethasone, was found to be well-tolerated and effective in preventing CINV in patients receiving HEC, including high-dose cisplatin.

• A risk of bias exists because of the sample characteristics.
• Although the two groups had comparable numbers of individuals with a history of vomiting during pregnancy and previous treatment with cisplatin, the fosaprepitant group had slightly more individuals with a history of motion sickness, which is associated with higher susceptibility to nausea and vomiting. 
• The fosaprepitant group had slightly more individuals with alcohol use, which is associated with slightly less nausea.  
• Women are known to experience more acute nausea and vomiting than do men. In this study, 76% of the population was men.

The use of single-dose fosaprepitant (150 mg) in combination with granisetron and dexamethasone has shown effectiveness in preventing nausea and vomiting in patients receiving highly emetogenic antineoplastic therapies, such as cisplatin.