Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy

Purpose: This analysis evaluated whether the antiemetic efficacy of the NK1 receptor antagonist aprepitant (EMEND(R), 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 I 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 = 8 1); 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. (C) 2003 by American Society of Clinical Oncology.