Addition of the Oral NK 1 Antagonist Aprepitant to Standard Antiemetics Provides Protection Against Nausea and Vomiting During Multiple Cycles of Cisplatin-Based Chemotherapy

• Published in: Journal of clinical oncology Vol. 21; no. 22; pp. 4105 - 4111
• Main Authors: de Wit, R., Herrstedt, J., Rapoport, B., Carides, A.D., Carides, G., Elmer, M., Schmidt, C., Evans, J.K., Horgan, K.J.
• Format: Journal Article
• Language: English
• Published: 15-11-2003
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2003.10.128

Purpose: This analysis evaluated whether the antiemetic efficacy of the NK
1
receptor antagonist aprepitant (EMEND
™
, 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/m
2
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.