Supportive Care in Cancer

, Volume 18, Issue 4, pp 423–431 | Cite as

Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study

  • Bernardo L. Rapoport
  • Karin Jordan
  • Judith A. BoiceEmail author
  • Arlene Taylor
  • Carole Brown
  • James S. Hardwick
  • Alexandra Carides
  • Timothy Webb
  • Hans-Joachim Schmoll
Original Article



Aprepitant was shown previously to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving an anthracycline and cyclophosphamide (AC)-based regimen. This study assessed aprepitant in patients receiving a broad range of MEC regimens with a variety of tumor types.


This phase III, randomized, gender-stratified, double-blind trial enrolled patients with confirmed malignancies, naïve to MEC or highly emetogenic chemotherapy, who were scheduled to receive a single dose of at least one MEC agent. Patients received an aprepitant triple-therapy regimen (aprepitant, ondansetron, and dexamethasone) or a control regimen (ondansetron and dexamethasone) administered orally. Primary and key secondary efficacy endpoints were proportions of patients with no vomiting and complete response (no vomiting and no rescue medication), respectively, during the 120 h post-chemotherapy.


Of 848 randomized patients, 77% were female, and 52% received non-AC-based antineoplastic regimens. Significantly, more patients in the aprepitant group achieved no vomiting and complete response, regardless of whether they received AC or non-AC regimens, in the 120 h after chemotherapy. Overall, the incidences of adverse events were generally similar in the aprepitant (62.8%) and control groups (67.2%).


The aprepitant regimen provided superior efficacy in the treatment of CINV in a broad range of patients receiving MEC (non-AC or AC) in both no vomiting and complete response endpoints. Aprepitant was generally well tolerated. These results show the benefit of including aprepitant as part of the standard antiemetic regimen for cancer patients receiving MEC.


Aprepitant NK1 antagonist Moderately emetogenic chemotherapy MEC Nausea and vomiting CINV 



This study was funded by Merck & Co., Inc., manufacturer of aprepitant. The authors wish to acknowledge Dr.’s Theodore Reiss and Stuart Green for contributions to the protocol design and Dr. Reiss for guidance throughout the course of the study.

Conflicts of interest

J.A.B., A.T., C.B., J.S.H., and A.C. are employees of Merck & Co., Inc. who may own stock and/or hold stock options in the Company. B.L.R., K. J., and H.J.S. have served as scientific advisors to Merck & Co., Inc.


  1. 1.
    Sun CC, Bodurka DC, Weaver CB, Rasu R, Wolf JK, Bevers MW, Smith JA, Wharton JT, Rubenstein EB (2005) Rankings and symptom assessments of side effects from chemotherapy: insights from experienced patients with ovarian cancer. Support Care Cancer 13(4):219–227CrossRefPubMedGoogle Scholar
  2. 2.
    Oo TH, Hesketh PJ (2005) Drug insight: new antiemetics in the management of chemotherapy-induced nausea and vomiting. Nat Clin Pract Oncol 2(4):196–201CrossRefPubMedGoogle Scholar
  3. 3.
    Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, Aapro MS, Gandara D, Lindley CM (1997) Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 15(1):103–109PubMedGoogle Scholar
  4. 4.
    Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24(18):2932–2947CrossRefPubMedGoogle Scholar
  5. 5.
    Roila F, Fatigoni S (2006) New antiemetic drugs. Ann Oncol 17(Suppl 2ii):96–100Google Scholar
  6. 6.
    Jordan K, Sippel C, Schmoll HJ (2007) Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. Oncologist 12(9):1143–1150CrossRefPubMedGoogle Scholar
  7. 7.
    Campos D, Pereira JR, Reinhardt RR, Carracedo C, Poli S, Vogel C, Martinez-Cedillo J, Erazo A, Wittreich J, Eriksson LO, Carides AD, Gertz BJ (2001) Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol 19(6):1759–1767PubMedGoogle Scholar
  8. 8.
    Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, Chawla SP, Carides AD, Ianus J, Elmer ME, Evans JK, Beck K, Reines S, Horgan KJ (2003) The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin—the Aprepitant Protocol 052 Study Group. J Clin Oncol 21(22):4112–4119CrossRefPubMedGoogle Scholar
  9. 9.
    Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie MG, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F (2003) Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97(12):3090–3098CrossRefPubMedGoogle Scholar
  10. 10.
    Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23(12):2822–2830CrossRefPubMedGoogle Scholar
  11. 11.
    Ihbe-Heffinger A, Ehlken B, Bernard R, Berger K, Peschel C, Eichler HG, Deuson R, Thodtmann J, Lordick F (2004) The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol 15(3):526–536CrossRefPubMedGoogle Scholar
  12. 12.
    McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, Hesney M, Lines CR, Petty KJ, Deutsch PJ, Murphy MG, Gottesdiener KM, Goldwater DR, Blum RA (2003) Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharmacol Ther 74(1):17–24CrossRefPubMedGoogle Scholar
  13. 13.
    Hochberg Y, Tamhane AC (1987) Multiple comparison procedures. Wiley, New YorkCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Bernardo L. Rapoport
    • 1
  • Karin Jordan
    • 2
  • Judith A. Boice
    • 3
    Email author
  • Arlene Taylor
    • 4
  • Carole Brown
    • 4
  • James S. Hardwick
    • 4
  • Alexandra Carides
    • 4
  • Timothy Webb
    • 5
  • Hans-Joachim Schmoll
    • 2
  1. 1.Medical Oncology Center of RosebankJohannesburgSouth Africa
  2. 2.Departments of Internal Medicine and Oncology/HematologyMartin-Luther-University of Halle-WittenbergHalle/SaaleGermany
  3. 3.Merck Research LaboratoriesRahwayUSA
  4. 4.Merck Research LaboratoriesUpper GwyneddUSA
  5. 5.Genesis Cancer CenterHot SpringsUSA

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