Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and emesis over multiple cycles of moderately emetogenic chemotherapy

Authors

  • Jørn Herrstedt M.D.,

    Corresponding author
    1. Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark
    • Department of Oncology 54 B1, Copenhagen University Hospital, DK-2730 Herlev, Denmark
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    • Fax: (011) 45-4453-3076

  • Hyman B. Muss M.D.,

    1. Vermont Cancer Center, University of Vermont, UHC Campus/St. Joseph, Burlington, Vermont
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  • David G. Warr M.D.,

    1. Department of Medical Oncology, Princess Margaret Hospital, Toronto, Ontario, Canada
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  • Paul J. Hesketh M.D.,

    1. Division of Hematology/Oncology, Caritas St. Elizabeth's Medical Center of Boston, Boston, Massachusetts
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  • Peter D. Eisenberg M.D.,

    1. California Cancer Care, Greenbrae, California
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  • Harry Raftopoulos M.D.,

    1. Department of Medicine, Columbia University, New York, New York
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  • Steven M. Grunberg M.D.,

    1. Vermont Cancer Center, University of Vermont, UHC Campus/St. Joseph, Burlington, Vermont
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  • Munir Gabriel Ph.D., M.B.A.,

    1. Merck & Co., Inc., West Point, Pennsylvania
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  • Anthony Rodgers M.S.,

    1. Merck & Co., Inc., West Point, Pennsylvania
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  • Carolyn M. Hustad Ph.D.,

    1. Merck & Co., Inc., West Point, Pennsylvania
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  • Kevin J. Horgan M.D.,

    1. Merck & Co., Inc., West Point, Pennsylvania
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  • Franck Skobieranda M.D.,

    1. Merck & Co., Inc., West Point, Pennsylvania
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  • on behalf of the Aprepitant Moderately Emetogenic Chemotherapy Study Group

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    • Participating investigators of the Aprepitant MEC Study Group (Protocol 071) were Anita Aggarwal, Francis P. Arena, Roy Beveridge, Ruemu Birhiray, Albert Brady, Elmer Brestan, Goran Broketa, Patrick Byrne, Elber Camacho, Robert Carroll, Javier Cassinello Espinosa, Veena Charu, Sant Chawla, Naveed Chowhan, Antonio Contu, Giorgio Cruciani, Bruno Daniele, Christopher Desch, David Dodwell, Andreas du Bois, Peter D. Eisenberg, Ira Felman, Susan Ferguson, Barry Fernbach, Michael Garcia, Pere Gascon-Vilaplana, Debjani Grenier, Alan Grosset, Thomas H. Grote, Rasim Gucalp, Troy Guthrie, Jr., Nadia Harbeck, Fred Hendler, Paul J. Hesketh, Hans-Fokke Hinrichs, David Irwin, Carlos Jara Sanchez, Haresh Jhangiani, Michael Jones, Glen Justice, Haralabos Kalofonos, Harvey Katzen, Peter Kennedy, Ali Khojasteh, Giorgio Lelli, Ana Maria Lopez, Susan L. Luedke, Alex Makalinao, Luigi Manzione, Orlando Martelo, Salvador Martin Algarra, Joaquin Montalar Salcedo, Hyman Muss, Ian N. Olver, Phatama Padavanija, Ravi Patel, Kelly B. Pendergrass, John Petrus, Tamas Pinter, Theodore Pollock, Cary Presant, Robert Pritchard, Ghulam Qureshi, Harry Raftopolous, Timothy Rearden, Sergio Ricci, Sylvia Richey, Edgardo Rivera, Fausto Roila, Mark A. Rosenthal, Bruce Saidman, Helmut Samonigg, Manuel Santiago, Hans-Joachim Schmoll, Lee Schwartzberg, Christopher Seidler, Stuart Selonick, Barbara Shea, David Shiba, Günther Steger, Steven Stein, Alan Stewart, Mark Taylor, Michael Thirlwell, Laszlo Thurzo, David Warr, Michael Wax, Roy T. Webb, Tracey Weisberg, Lorrin Yee, Sharon J. Yee, Louise Yelle, Winnie Yeo, Robert Zielinski.


Abstract

BACKGROUND

An aprepitant (APR) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles.

METHODS

The authors performed a randomized, double-blind study. Eligible patients with breast carcinoma were naïve to emetogenic chemotherapy and treated with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND] 8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2–3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2–3: OND 8 mg twice per day). Data on nausea, emesis, and use of rescue medication were collected. The primary end point was the proportion of patients with a complete response (CR; no emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple-cycle extension were the probabilities of a CR in Cycles 2–4 and a sustained CR rate across multiple cycles.

RESULTS

Of 866 patients randomized, 744 (85.9%) entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles. Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus 39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for Cycle 4. The cumulative percentage of patients with a sustained CR over all 4 cycles was greater with the APR regimen (P = 0.017).

CONCLUSIONS

The APR regimen was more effective than a control regimen for the prevention of nausea and emesis induced by MEC over multiple chemotherapy cycles. Cancer 2005. © 2005 American Cancer Society.

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