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Amisulpride prevents nausea and vomiting associated with highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled, dose-ranging trial

  • J. HerrstedtEmail author
  • Y. Summers
  • K. Jordan
  • J. von Pawel
  • A. H. Jakobsen
  • M. Ewertz
  • S. Chan
  • J. D. Naik
  • M. Karthaus
  • S. Dubey
  • R. Davis
  • G. M. Fox
Original Article

Abstract

Purpose

Chemotherapy-induced nausea and vomiting (CINV) remain significant clinical problems, especially in the delayed phase (24–120 h after chemotherapy). Amisulpride is a dopamine D2/D3-receptor antagonist previously shown to be an effective intravenous antiemetic. We conducted a randomised, double-blind study to characterise the dose response of oral amisulpride in delayed phase CINV.

Methods

Chemotherapy-naïve patients receiving cisplatin ≥ 70 mg/m2 or an anthracycline-cyclophosphamide regimen for breast cancer received, on day 1, 20 mg amisulpride and 8–16 mg ondansetron intravenously followed, once daily on days 2–4, by 10, 20 or 40 mg oral amisulpride or placebo. A control group receiving standard three-drug prophylaxis was enrolled for assay sensitivity purposes. The primary endpoint was complete response (CR), defined as no emesis or rescue medication use, in the delayed phase.

Results

Three hundred eighteen subjects were evaluable per protocol. CR rate (24–120 h) was 20% with placebo and 46% with 10 mg amisulpride (p = 0.006 after multiplicity adjustment); in the three-drug control group, it was 59%. Emesis, nausea and 0–120-h CR rate were significantly improved with 10 mg amisulpride compared to placebo. Higher doses of amisulpride were not more effective than 10 mg. In patients with acute phase CR, delayed phase CR rate was 44% for placebo, 75% for 10 mg amisulpride (p = 0.022) and 70% for the 3-drug control. No significant differences were seen between groups in safety parameters.

Conclusions

Amisulpride 10 mg orally is safe and superior to placebo at preventing delayed CINV caused by highly emetogenic chemotherapy.

Trial registration

NCT01857232

Keywords

Amisulpride Nausea Vomiting Chemotherapy Cisplatin Anthracycline-cyclophosphamide 

Notes

Acknowledgements

Editorial assistance was provided by Peter Bates of Cambridge Medical Writing Services, UK.

Authors’ contributions

The protocol was drafted by Gabriel Fox and Jørn Herrstedt and all authors contributed to the final version. All other authors included patients in the study. A draft manuscript was prepared by Jørn Herrstedt and Gabriel Fox and finally reviewed and approved by all authors.

Funding

This study was financially funded by Acacia Pharma Ltd., Cambridge, UK.

Compliance with ethical standards

The protocol was approved by independent ethics committees at each site/country (25 sites and 3 countries) and the study was conducted in accordance with Good Clinical Practice and with the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from all individual participants included in the study.

Conflict of interest

Gabriel Fox is an employee and stockholder of Acacia Pharma Ltd.

Karin Jordan has received honoraria for advisory board meetings and/or presentations for Merck, MSD, Helsinn, Tesaro, Amgen, Hexal and Pfizer.

No other potential conflicts are disclosed.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • J. Herrstedt
    • 1
    • 2
    Email author return OK on get
  • Y. Summers
    • 3
  • K. Jordan
    • 4
    • 5
  • J. von Pawel
    • 6
  • A. H. Jakobsen
    • 7
  • M. Ewertz
    • 1
  • S. Chan
    • 8
  • J. D. Naik
    • 9
  • M. Karthaus
    • 10
  • S. Dubey
    • 11
  • R. Davis
    • 12
  • G. M. Fox
    • 13
  1. 1.Department of Oncology, Odense University Hospital, Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  2. 2.Department of Clinical OncologyZealand University HospitalRoskildeDenmark
  3. 3.Pulmonary Oncology UnitUniversity Hospital of South ManchesterManchesterUK
  4. 4.Department of Oncology/HaematologyHalle (Saale) University ClinicHalle (Saale)Germany
  5. 5.Department of Medicine V, Hematology, Oncology and RheumatologyUniversity of HeidelbergHeidelbergGermany
  6. 6.Pulmonology Clinic, Asklepios Specialist ClinicMunichGermany
  7. 7.Department of OncologyHerlev University HospitalCopenhagenDenmark
  8. 8.Academic Unit of OncologyNottingham University HospitalsNottinghamUK
  9. 9.Department of Medical Oncology, Mid Yorkshire NHS TrustWakefieldUK
  10. 10.Haematology, Oncology and Palliative Medicine DepartmentNeuperlach ClinicMunichGermany
  11. 11.Department of OncologyDerriford HospitalPlymouthUK
  12. 12.Cancer Clinical Trials OfficeWexham Park HospitalSloughUK
  13. 13.Department of Clinical Development, Acacia Pharma LtdCambridgeUK

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