Originally published as JCO Early Release 10.1200/JCO.2003.10.128 on October 14 2003

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Addition of the Oral NK₁ Antagonist Aprepitant to Standard Antiemetics Provides Protection Against Nausea and Vomiting During Multiple Cycles of Cisplatin-Based Chemotherapy

R. de Wit, J. Herrstedt, B. Rapoport, A.D. Carides, G. Carides, M. Elmer, C. Schmidt, J.K. Evans, K.J. Horgan

From the Rotterdam Cancer Institute, Rotterdam, The Netherlands; Copenhagen University Hospital, Herlev, Denmark; The Medical Oncology Centre of Rosebank, Johannesburg, S Africa; and Merck Research Laboratories, West Point, PA.

Address reprint requests to Ronald De Wit, MD, PhD, Department of Medical Oncology, Rotterdam Cancer Institute/Erasmus University Medical Center, P.O. Box 5201, 3008 Rotterdam, The Netherlands; e-mail: r.dewit{at}erasmusmc.nl.

Purpose: This analysis evaluated whether the antiemetic efficacy of the NK₁ receptor antagonist aprepitant (EMEND^TM, Merck, Whitehouse Station, NJ) plus standard antiemetics could be sustained for up to six cycles of cisplatin-based chemotherapy.

Patients and Methods: Patients receiving cisplatin 70 mg/m² were blindly assigned to receive one of the following three regimens: (1) aprepitant 375 mg 1 hour before cisplatin on day 1 and aprepitant 250 mg on days 2 to 5 (n = 35); (2) aprepitant 125 mg before cisplatin and aprepitant 80 mg on days 2 to 5 (n = 81); or (3) placebo before cisplatin on days 2 to 5 (n = 86). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 5. The primary end point was complete response (no emesis and no rescue therapy) over 5 days following cisplatin in up to six cycles. A cumulative probability analysis using a model for transitional probabilities was used to analyze the data. The aprepitant 375/250-mg regimen was discontinued early in light of new pharmacokinetic data.

Results: In the first cycle, 64% of patients in the aprepitant group and 49% in the standard therapy group had a complete response. Thereafter, complete response rates for the aprepitant group were still 59% by cycle 6, but decreased to 34% by cycle 6 for the standard therapy group. Reasons for discontinuation were similar across treatment groups.

Conclusion: Compared with patients who received standard therapy, those who received only the aprepitant regimen had better and more sustained protection against chemotherapy-induced nausea and vomiting over multiple cycles.

Funded by Merck Research Laboratories, the manufacturer of aprepitant.

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