Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: Randomized, double-blind study protocol-EASE

Steven Grunberg, Daniel Chua, Anish Maru, José Dinis, Suzanne DeVandry, Judith A. Boice, James S. Hardwick, Elizabeth Beckford, Arlene Taylor, Alexandra Carides, Fausto Roila, Jørn Herrstedt

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant. Patients and Methods A randomized, double-blind, active-control design was used to test whether fosaprepitant isnoninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m2 for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points. Results A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively). Conclusion Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.

    OriginalsprogEngelsk
    Sider (fra-til)1495-1501
    Antal sider7
    TidsskriftJournal of Clinical Oncology
    Vol/bind29
    Udgave nummer11
    DOI
    StatusUdgivet - 10 apr. 2011

    Fingeraftryk Udforsk hvilke forskningsemner 'Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: Randomized, double-blind study protocol-EASE' indeholder.

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