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Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study

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Abstract

Purpose

The primary objective was to determine if a single dose of casopitant 90 mg added to ondansetron and dexamethasone would improve the control of chemotherapy-induced nausea and vomiting (CINV) over 0–120 h following initiation of oxaliplatin-based moderately emetic chemotherapy (MEC) compared to ondansetron and dexamethasone alone.

Methods

Patients with colorectal cancer received either casopitant or placebo intravenously (IV) added to ondansetron 8 mg bid oral on study days 1 to 3 and one dose of dexamethasone 8 mg IV given prior to starting the oxaliplatin on day 1. The primary endpoint was the percentage of subjects achieving complete response (CR; no vomiting/retching or use of rescue medication) during 120 h after initiation of chemotherapy in cycle 1.

Results

No difference in the rate of CR was noted in the casopitant group compared to the placebo group for the overall (placebo 85%, casopitant 86%, p = 0.7273), acute (placebo 96%, casopitant 97%), or delayed phases (placebo 85%, casopitant 86%). The average area under curve (0–∞) of casopitant after a single 90-mg IV dose was 8,390 ng h/mL. At 24 h after casopitant 90-mg IV dosing, the plasma casopitant concentration was 24% lower than the values noted in prior studies with 150 mg oral administration, and the plasma exposure of the major metabolite (GSK525060) was 18% lower.

Conclusions

Addition of single-dose casopitant 90 mg IV did not improve the control of CINV at any time during 120 h following initiation of oxaliplatin-based MEC. Excellent control of CINV was achieved in this study population with the combination of ondansetron and dexamethasone alone.

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Acknowledgments

Editorial support was provided by Ann Sherwood, PhD, at Publication CONNEXION and was funded by GlaxoSmithKline (NCT00601172). All listed authors meet the criteria for authorship set forth by the International Committee for Medical Journal Editors. The authors wish to acknowledge the following individuals for their contributions and critical review during the development of this manuscript: Simon Thorn, PhD.

Conflict of interest

S.L., M.R., J.L., and O.W. receive remuneration from GSK. S.L. and M.R. may own stock and/or hold stock options in the company. P.D. is a consultant and/or holds an advisory role for Sanofi Aventis, Novartis, Roche, and AstraZeneca. P.H. is a consultant and/or holds an advisory role for Merck, Eisai, Hellsin, and GSK. P.H. receives funding from Merck and Eisai.

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Authors and Affiliations

  1. Department of Hematology and Oncology, Lahey Clinic Medical Center, Burlington, MA, 01805, USA

    Paul J. Hesketh

  2. GSK Research and Development, 1250 South Collegeville Road, Collegeville, PA, 19426, USA

    Oliver Wright, Mark Russo, Jeremey Levin & Stephen Lane

  3. Medical Oncology Unit, S. Carlo Hospital, Via P. Petrone, 1, 85100, Potenza, Italy

    Gerardo Rosati

  4. Petrov Research Institute of Oncology, Leningradskaya Street 68 Pesochny-2, 197758, Saint Petersburg, Russia

    Vladimir Moiseyenko

  5. Hôpital Maisonneuve-Rosemont, Université de Montréal, 5415 boul. l’Assomption, Montréal, QC, H1T 2M4, Canada

    Pierre Dube

  6. Samara Regional Oncology Center, Samara, 443066, Russian Federation

    Mikhail Kopp

  7. Stavropol Regional Oncology Center, Stavropol, 355047, Russian Federation

    Anatoly Makhson

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  1. Paul J. Hesketh
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Correspondence to Paul J. Hesketh.

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Hesketh, P.J., Wright, O., Rosati, G. et al. Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind, active-controlled, two arm, parallel group study. Support Care Cancer 20, 1471–1478 (2012). https://doi.org/10.1007/s00520-011-1235-4

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  • DOI: https://doi.org/10.1007/s00520-011-1235-4

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