Originally published as JCO Early Release 10.1200/JCO.2003.01.095 on October 14 2003

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hesketh, P. J. Articles by Horgan, K. J. Search for Related Content PubMed PubMed Citation Articles by Hesketh, P. J. Articles by Horgan, K. J. Social Bookmarking                            What's this?

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

Paul J. Hesketh, Steven M. Grunberg, Richard J. Gralla, David G. Warr, Fausto Roila, Ronald de Wit, Sant P. Chawla, Alexandra D. Carides, Juliana Ianus, Mary E. Elmer, Judith K. Evans, Klaus Beck, Scott Reines, Kevin J. Horgan

From the Caritas St Elizabeth’s Medical Center, Brighton, MA; University of Vermont, UHC Campus/St Joseph, Burlington, VT; New York Lung Cancer Alliance, New York, NY; Princess Margaret Hospital, Toronto, Ontario, Canada; Policlinico Monteluce, Divisione Oncologica Medica Ospedale Policlinico, Perugia, Italy; Rotterdam Cancer Institute and University Hospital, Groene Hilledijk, Rotterdam, the Netherlands; Century City Hospital, Los Angeles, CA; and Merck Research Laboratories, Blue Bell, PA.

Address reprint requests to Paul Hesketh, MD, Caritas St Elizabeth’s Medical Center, 736 Cambridge St, Brighton, MA 02135-2997; e-mail: phesketh{at}massmed.org.

Purpose: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV).

Patients and Methods: Patients receiving cisplatin 70 mg/m² for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments.

Results: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P < .001 for all three comparisons).

Conclusion: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

This study was funded by Merck Research Laboratories, Whitehouse Station, NJ.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				J. Herrstedt, W. Apornwirat, A. Shaharyar, Z. Aziz, F. Roila, S. Van Belle, M. W. Russo, J. Levin, S. Ranganathan, M. Guckert, et al. Phase III Trial of Casopitant, a Novel Neurokinin-1 Receptor Antagonist, for the Prevention of Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy J. Clin. Oncol., November 10, 2009; 27(32): 5363 - 5369. [Abstract] [Full Text] [PDF]

				F. Roila, J. Rolski, R. Ramlau, M. Dediu, M. W. Russo, R. R. Bandekar, and S. M. Grunberg Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting Ann. Onc., November 1, 2009; 20(11): 1867 - 1873. [Abstract] [Full Text] [PDF]

				R. J. Gralla and H. Raftopoulos Progress in the Control of Chemotherapy-Induced Emesis: New Agents and New Studies J. Oncol. Pract, May 1, 2009; 5(3): 130 - 133. [Full Text] [PDF]

				K. TAGUCHI, H. IIHARA, M. ISHIHARA, Y. KOMORI, K. TANIZAWA, K. MATSUURA, and Y. ITOH Comparison of Antiemetic Efficacy between Single and Repeated Treatments with a 5-HT3 Receptor Antagonist in Breast Cancer Patients with High-risk Emetogenic Chemotherapy Anticancer Res, May 1, 2009; 29(5): 1721 - 1725. [Abstract] [Full Text] [PDF]

				A. Jarkowski III Possible contribution of aprepitant to ifosfamide-induced neurotoxicity Am. J. Health Syst. Pharm., December 1, 2008; 65(23): 2229 - 2231. [Abstract] [Full Text] [PDF]

				M. Okumura, R. Arakawa, H. Ito, C. Seki, H. Takahashi, H. Takano, E. Haneda, R. Nakao, H. Suzuki, K. Suzuki, et al. Quantitative Analysis of NK1 Receptor in the Human Brain Using PET with 18F-FE-SPA-RQ J. Nucl. Med., November 1, 2008; 49(11): 1749 - 1755. [Abstract] [Full Text] [PDF]

				R. B Ibrahim, M. H Abidi, L. J Ayash, S. M Cronin, C. Cadotte, J. Mulawa, P. A Jacobson, D. W Smith, J. P Uberti, and D. J Edwards Effect of aprepitant on intravenous tacrolimus disposition in reduced intensity hematopoietic stem cell transplantation Journal of Oncology Pharmacy Practice, September 1, 2008; 14(3): 113 - 121. [Abstract] [PDF]

				A. Naeim, S. M. Dy, K. A. Lorenz, H. Sanati, A. Walling, and S. M. Asch Evidence-Based Recommendations for Cancer Nausea and Vomiting J. Clin. Oncol., August 10, 2008; 26(23): 3903 - 3910. [Abstract] [Full Text] [PDF]

				J. Xu, F. Xu, and E. Barrett Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice Am J Physiol Lung Cell Mol Physiol, July 1, 2008; 295(1): L162 - L170. [Abstract] [Full Text] [PDF]

				P. J. Hesketh Chemotherapy-Induced Nausea and Vomiting N. Engl. J. Med., June 5, 2008; 358(23): 2482 - 2494. [Full Text] [PDF]

				K. Jordan, C. Sippel, and H.-J. Schmoll Guidelines for Antiemetic Treatment of Chemotherapy-Induced Nausea and Vomiting: Past, Present, and Future Recommendations Oncologist, September 1, 2007; 12(9): 1143 - 1150. [Abstract] [Full Text] [PDF]

				K. C. Lasseter, J. Gambale, B. Jin, A. Bergman, M. Constanzer, J. Dru, T. H. Han, A. Majumdar, J. K. Evans, and M. G. Murphy Tolerability of Fosaprepitant and Bioequivalency to Aprepitant in Healthy Subjects J. Clin. Pharmacol., July 1, 2007; 47(7): 834 - 840. [Abstract] [Full Text] [PDF]

				A. K. Majumdar, K. X. Yan, D. V. Selverian, S. Barlas, M. Constanzer, J. Dru, J. B. McCrea, T. Ahmed, G. S. Frick, W. K. Kraft, et al. Effect of Aprepitant on the Pharmacokinetics of Intravenous Midazolam J. Clin. Pharmacol., June 1, 2007; 47(6): 744 - 750. [Abstract] [Full Text] [PDF]

				D. L. Robinson and B. A. Carr Delayed Vomiting in Children With Cancer After Receiving Moderately High or Highly Emetogenic Chemotherapy Journal of Pediatric Oncology Nursing, March 1, 2007; 24(2): 70 - 80. [Abstract] [PDF]

				B. A. Chizh, M. Gohring, A. Troster, G. K. Quartey, M. Schmelz, and W. Koppert Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers Br. J. Anaesth., February 1, 2007; 98(2): 246 - 254. [Abstract] [Full Text] [PDF]

				G. M Higa, M. L Auber, R. Altaha, D. Piktel, S. Kurian, G. Hobbs, and K. Landreth 5-Hydroxyindoleacetic acid and substance P profiles in patients receiving emetogenic chemotherapy Journal of Oncology Pharmacy Practice, December 1, 2006; 12(4): 201 - 209. [Abstract] [PDF]

				S. X. Li, E. Pequignot, D. Panebianco, P. Lupinacci, A. Majumdar, L. Rosen, T. Ahmed, J. E. Royalty, T. H. Rushmore, M. G. Murphy, et al. Lack of Effect of Aprepitant on Hydrodolasetron Pharmacokinetics in CYP2D6 Extensive and Poor Metabolizers. J. Clin. Pharmacol., July 1, 2006; 46(7): 792 - 801. [Abstract] [Full Text] [PDF]

				M. G. Kris, P. J. Hesketh, M. R. Somerfield, P. Feyer, R. Clark-Snow, J. M. Koeller, G. R. Morrow, L. W. Chinnery, M. J. Chesney, R. J. Gralla, et al. American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006 J. Clin. Oncol., June 20, 2006; 24(18): 2932 - 2947. [Abstract] [Full Text] [PDF]

				H. J. Schmoll, M. S. Aapro, S. Poli-Bigelli, H.-K. Kim, K. Park, K. Jordan, J. von Pawel, H. Giezek, T. Ahmed, and C. Y. Chan Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment Ann. Onc., June 1, 2006; 17(6): 1000 - 1006. [Abstract] [Full Text] [PDF]

				A. K. Majumdar, L. Howard, M. R. Goldberg, L. Hickey, M. Constanzer, P. L. Rothenberg, T. M. Crumley, D. Panebianco, T. E. Bradstreet, A. J. Bergman, et al. Pharmacokinetics of aprepitant after single and multiple oral doses in healthy volunteers. J. Clin. Pharmacol., March 1, 2006; 46(3): 291 - 300. [Abstract] [Full Text] [PDF]

				The Antiemetic Subcommittee of the Multinational A Prevention of chemotherapy- and radiotherapy-induced emesis: results of the 2004 Perugia International Antiemetic Consensus Conference Ann. Onc., January 1, 2006; 17(1): 20 - 28. [Abstract] [Full Text] [PDF]

				M. T Holdsworth and T. Vo-Nguyen Employment of Substandard Antiemetic Prophylaxis in Recent Trials of Chemotherapy-Induced Nausea and Vomiting Ann. Pharmacother., November 1, 2005; 39(11): 1903 - 1910. [Abstract] [Full Text] [PDF]

				D. G. Warr, P. J. Hesketh, R. J. Gralla, H. B. Muss, J. Herrstedt, P. D. Eisenberg, H. Raftopoulos, S. M. Grunberg, M. Gabriel, A. Rodgers, et al. 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., April 20, 2005; 23(12): 2822 - 2830. [Abstract] [Full Text] [PDF]

				S. Singh, W. Parulekar, N. Murray, R. Feld, W. K. Evans, D. Tu, and F. A. Shepherd Influence of Sex on Toxicity and Treatment Outcome in Small-Cell Lung Cancer J. Clin. Oncol., February 1, 2005; 23(4): 850 - 856. [Abstract] [Full Text] [PDF]

				A. M Massaro and K. L Lenz Aprepitant: A Novel Antiemetic for Chemotherapy-Induced Nausea and Vomiting Ann. Pharmacother., January 1, 2005; 39(1): 77 - 85. [Abstract] [Full Text] [PDF]

				E S Antonarakis and R D W Hain Nausea and vomiting associated with cancer chemotherapy: drug management in theory and in practice Arch. Dis. Child., September 1, 2004; 89(9): 877 - 880. [Abstract] [Full Text] [PDF]

				M. G. Kris Why Do We Need Another Antiemetic? Just Ask. J. Clin. Oncol., November 15, 2003; 21(22): 4077 - 4080. [Full Text] [PDF]

				R. de Wit, J. Herrstedt, B. Rapoport, A.D. Carides, G. Carides, M. Elmer, C. Schmidt, J.K. Evans, and K.J. Horgan Addition of the Oral NK1 Antagonist Aprepitant to Standard Antiemetics Provides Protection Against Nausea and Vomiting During Multiple Cycles of Cisplatin-Based Chemotherapy J. Clin. Oncol., November 15, 2003; 21(22): 4105 - 4111. [Abstract] [Full Text] [PDF]