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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4112-4119
Number of pages8
JournalJournal of Clinical Oncology
Volume21
Issue number22
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

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aprepitant
Nausea
Cisplatin
Vomiting
Placebos
Dexamethasone
Drug Therapy
Ondansetron
Logistic Models
Therapeutics
Serotonin Antagonists
Antiemetics
Group Psychotherapy
Adrenal Cortex Hormones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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

In: Journal of Clinical Oncology, Vol. 21, No. 22, 15.11.2003, p. 4112-4119.

Research output: Contribution to journalArticle

Hesketh, Paul J. ; Grunberg, Steven M. ; Gralla, Richard J. ; Warr, David G. ; Roila, Fausto ; De Wit, Ronald ; Chawla, Sant P. ; Carides, Alexandra D. ; Ianus, Juliana ; Elmer, Mary E. ; Evans, Judith K. ; Beck, Klaus ; Reines, Scott ; Horgan, Kevin J. / 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. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 22. pp. 4112-4119.
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abstract = "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.",
author = "Hesketh, {Paul J.} and Grunberg, {Steven M.} and Gralla, {Richard J.} and Warr, {David G.} and Fausto Roila and {De Wit}, Ronald and Chawla, {Sant P.} and Carides, {Alexandra D.} and Juliana Ianus and Elmer, {Mary E.} and Evans, {Judith K.} and Klaus Beck and Scott Reines and Horgan, {Kevin J.}",
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T1 - The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting

T2 - A multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin - The Aprepitant Protocol 052 Study Group

AU - Hesketh, Paul J.

AU - Grunberg, Steven M.

AU - Gralla, Richard J.

AU - Warr, David G.

AU - Roila, Fausto

AU - De Wit, Ronald

AU - Chawla, Sant P.

AU - Carides, Alexandra D.

AU - Ianus, Juliana

AU - Elmer, Mary E.

AU - Evans, Judith K.

AU - Beck, Klaus

AU - Reines, Scott

AU - Horgan, Kevin J.

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Y1 - 2003/11/15

N2 - 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.

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