Takahashi, T., Hoshi, E., Takagi, M., Katsumata, N., Kawahara, M., & Eguchi, K. (2010). Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin. Cancer Science, 101, 2455–2461.

To evaluate the efficacy and safety of aprepitant plus standard therapy (granisetron and dexamethasone) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in Japanese patients with cancer undergoing treatment with chemotherapy including a highly emetogenic cisplatin-based regimen (≥ 70 mg/m²)

Patients were allocated to three groups.

• The aprepitant 125/80 mg group received 125 mg on day 1 and a dose of 80 mg on days 2–5.
• The aprepitant 40/25 mg group received of 40 mg on day 1 and a dose of 25 mg on days 2–5.
• The standard therapy group received an oral administration of placebo on days 1–5.

All patients received standard therapy consisting of 40 µg/kg IV granisetron on day 1 and dexamethasone. Concomitant use of other antiemetics was prohibited from 48 hours before day 1 to the morning of day 6, except for rescue therapy for CINV.

• The study looked at 439 participants.
• Mean age for the 125/80 group was 60.5 years (SD = 9.7 years); for the 40/25 group, 63.3 years (SD = 9.4); and for the standard group, 62.2 years (SD = 9.8).
• Gender of patients was 24% female and 76% male.
• Patient diagnoses were
  • 72% respiratory
  • 15% urogenital
  • 5% digestive
  • 5% eyes/ears/nose/throat
  • 3% other
• Mean cisplatin dose (mg/m²) for the 125/80 group was 76.9; for the 40/25 group, 76.9; and for the standard group, 76.2.
• Percentage of patients with a history of morning sickness was 42%; 8% of patients had a history of motion sickness.
• Patients receiving cisplatin chemotherapy was 17%; chemotherapy except cisplatin, 21%, and CINV except cisplatin chemotherapy, 40%.

The study was conducted at multiple sites in Japan.

Study participants were in active treatment.

This was a phase II, placebo-controlled, double-blind, randomized parallel comparative study.

• Patients recorded in a symptom diary the onset of vomiting and nausea intensity on a 4-point scale, and the name and dose of any rescue therapy used along with the date and time from day 1 to the morning of day 6.
• Safety was evaluated based on physical examination findings (vital signs, weight, general lab tests, lab values).
• Toxicity was evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTAE).

In the three study groups, the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (standard therapy), 66.4% (aprepitant 40/25 mg), and 70.5% (aprepitant 125/80 mg). Efficacy was significantly higher in the aprepitant 40⁄25 mg and 125/80 mg groups than in the standard therapy group (p = 0.0053 and p = 0.0004, respectively), and efficacy was the highest is the aprepitant 125/80 mg group. The delayed phase efficacy was similar to the overall phase efficacy, indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. Aprepitant was generally well tolerated.

Aprepitant was shown to be more effective in the overall phase, including both acute and delayed, when compared to the standard group, irrespective of sex, age, or previous treatment with cisplatin.

• Limited information was provided regarding measurement tools.
• The potential for anticipatory nausea was not addressed, especially in patients who had received previous emetogenic therapies.

Aprepitant used in combination with 5-HT₃ receptor antagonists and a corticosteroid is effective in preventing CINV associated with highly emetogenic agents.