Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy‐induced nausea and vomiting
Authors: Poli‐Bigelli Sergio , Rodrigues‐Pereira Jose , Carides Alexandra D. , Julie Ma Guoguang , Eldridge Krista , Hipple Anita , Evans Judith K. , Horgan Kevin J. , Lawson Francesca ,   On behalf of the Aprepitant Protocol 054 Study Group
Published: May 2003

BACKGROUND

Aprepitant is a novel neurokinin 1 (NK1) antagonist that has been shown to improve control of chemotherapy‐induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5‐hydroxytriptamine‐3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial.

METHODS

This was a multicenter, randomized, double‐blind, placebo‐controlled, parallel‐groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high‐dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2–4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2–3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent‐to‐treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5‐day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability.

RESULTS

A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2–5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths.

CONCLUSIONS

In patients with cancer who are receiving high‐dose cisplatin‐based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2–3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated. Cancer 2003;97:3090–8. © 2003 American Cancer Society.

DOI 10.1002/cncr.11433