Skip to main content
SpringerLink
Log in

Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy: a dose-escalation study

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to investigate the antiemetic effect of the dopamine D2- and dopamine D3-receptor antagonist, amisulpride, in patients receiving cisplatin-based chemotherapy.

Methods

This dose-finding, non-comparative study investigated the antiemetic effect and safety of increasing doses (2.5, 7.5 and 20 mg) of amisulpride against acute nausea and vomiting in the period 0–24 h after initiation of cisplatin-based chemotherapy. The 20 mg dose was also investigated in combination with the 5-HT3-receptor antagonist, ondansetron. The primary parameter was complete response (0–24 h), defined as no emesis and no need for rescue antiemetics. Secondary parameters were number of emetic episodes, severity of nausea and time to first emetic episode and start of nausea.

Results

A total of 51 patients were enrolled and evaluable. None of the 10 patients in the 2.5 and 7.5 mg groups obtained a CR. In the 20 mg monotherapy cohort, two of the 18 subjects (11%) had a CR, 3/18 (17%) had no emesis and 12/18 (67%) had no significant nausea. Seven subjects (39%) had no nausea at all (a VAS score < 5 mm). In the combination (ondansetron plus amisulpride) cohort, 19/23 (83%; 90% confidence interval: 65–94%) had a CR and 14/23 (61%) had no nausea at all.

Conclusions

Amisulpride has antiemetic effect against cisplatin-induced acute nausea and vomiting. The effect against nausea is of particular interest. Randomised studies are warranted to further explore the effect and safety of amisulpride.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J (2006) Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol 24:4472–4478

    Article  CAS  Google Scholar 

  2. Kris MG, Gralla RJ, Clark RA, Tyson LB, O'Connell JP, Wertheim MS, Kelsen DP (1985) Incidence, course, and severity of delayed nausea and vomiting following the administration of high-dose cisplatin. J Clin Oncol 3:1379–1384

    Article  CAS  Google Scholar 

  3. Hesketh PJ (2008) Chemotherapy-induced nausea and vomiting. N Engl J Med 358:2482–2494

    Article  CAS  Google Scholar 

  4. Roila F, Molassiotis M, Herrstedt J, Aapro M, Gralla RJ, Bruera E, Clark-Snow RA, Dupuis LL, Einhorn LH, Feyer P, Hesketh PJ, Jordan K, Olver I, Rapoport BL, Roscoe J, Ruhlmann CH, Walsh D, Warr D, van der Wetering M on behalf of the participants of the MASCC/ESMO Consensus Conference Copenhagen 2015 (2016). 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients Ann Oncol 27 (supplement 5):v119-v133

  5. 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 21:4112–4119

    Article  CAS  Google Scholar 

  6. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Ma GJ, Eldridge K, Hipple A, Evans JK, Horgan KJ, Lawson F On behalf of the Aprepitant Protocol 054 Study Group (2003). Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Cancer 97:3090–3098

    Article  CAS  Google Scholar 

  7. Hesketh PJ, Rossi G, Rizzi G, Palmas M, Alyasova A, Bondarenko I, Lisyanskaya A, Gralla RJ (2014) Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol 25:1340–1346

    Article  CAS  Google Scholar 

  8. Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM (2015) Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol 16:1079–1089

    Article  CAS  Google Scholar 

  9. Moertel CG, Reitemeier RJ (1969) Controlled clinical studies of orally administered antiemetic drugs. Gastroenterology 57:262–268

    Article  CAS  Google Scholar 

  10. Grunberg SM, Gala KV, Lampenfeld M, Jamin D, Johnson K, Cariffe P, Strych D, Krailo M (1984) Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study. J Clin Oncol 2:782–787

    Article  CAS  Google Scholar 

  11. Roberts WS, Wisniewski BJ, Cavanagh D, Marsden DE (1985) Droperidol as an antiemetic in cis-platinum-induced nausea and vomiting. Oncology 42:42–43

    Article  CAS  Google Scholar 

  12. Olver IN, Laidlaw CR, Matthews JP, Bishop JF, Hayes AM, Wolf M, Toner GC (1994) A randomised double blind crossover study of domperidone and prochlorperazine suppositories for controlling emesis in outpatients receiving chemotherapy. Eur J Cancer 30A:426–429

    Article  CAS  Google Scholar 

  13. Stuart-Harris R, Buckman R, Starke I, Wiltshaw E (1983) Chlorpromazine, placebo and droperidol in the treatment of nausea and vomiting associated with cisplatin therapy. Postgrad Med J 59:500–503

    Article  CAS  Google Scholar 

  14. Herrstedt J, Sigsgaard T, Handberg J, Schousboe BMB, Hansen M, Dombernowsky P (1997) Randomized, double-blind comparison of ondansetron versus ondansetron plus metopimazine as antiemetic prophylaxis during platinum-based chemotherapy in patients with cancer. J Clin Oncol 15:1690–1696

    Article  CAS  Google Scholar 

  15. Herrstedt J (1998). Chemotherapy-induced nausea and vomiting with special emphasis on metopimazine. Dan Med Bull 45:412-22 (dissertation, University of Copenhagen)

  16. Darmani NA, Zhao W, Ahmad B (1999) The role of D2 and D3 dopamine receptors in the mediation of emesis in Cryptotis parva (the last shrew). J Neural Transm 106:1045–1061

    Article  CAS  Google Scholar 

  17. Coukell AJ, Spencer CM, Benfield P (1996) Amisulpride: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of schizophrenia. CNS Drugs 6:237–256

    Article  CAS  Google Scholar 

  18. Kranke P, Eberhart L, Motsch J, Chassard D, Wallenborn J, Diemunsch P, Liu N, Keh D, Bouaziz H, Bergis M, Fox G, Gan TJ (2013) I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial. Br J Anaesth 111:938–945

    Article  CAS  Google Scholar 

  19. Spina E, de Leon J (2007) Metabolic drug interactions with newer antipsychotics: a comparative review. Basic Clin Pharmacol Toxicol 100:4–22

    Article  CAS  Google Scholar 

  20. Coulouvrat C, Dondey-Nouvel L (1999) Safety of amisulpride (Solian): a review of 11 clinical studies. Int Clin Psychopharmacol 14:209–218

    Article  CAS  Google Scholar 

  21. Taubel J, Ferber G, Fox G, Fernandes S, Lorch U, Camm AJ (2016) Thorough QT study of the effect of intravenous amisulpride on QTc interval in Caucasian and Japanese healthy subjects. Br J Clin Pharmacol. doi:10.1111/bcp.13128

    Article  Google Scholar 

  22. Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10

    Article  CAS  Google Scholar 

  23. Abbas AI, Hedlund PB, Huang XP, Tran TB, Meltzer HY, Roth BL (2009) Amisulpride is a potent 5-HT7 antagonist: relevance for antidepressant actions in vivo. Psychopharmacology 205:119–128

    Article  CAS  Google Scholar 

  24. Roila F, Tonato M, Cognetti F, Cortesi E, Favalli G, Marangolo M, Amadori D, Bella MA, Gramazio V, Donati D, Ballatori E, Del Favero A (1991) Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol 9:675–678

    Article  CAS  Google Scholar 

  25. Smyth JF, Coleman RE, Nicolson M, Gallmeier WM, Leonard RCF, Cornbleet MA, Allan SG, Upadhyaya BK, Bruntsch U (1991) Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron? BMJ 303:1423–1426

    Article  CAS  Google Scholar 

  26. Marty M, Pouillart P, Scholl S, Droz JP, Azab M, Brion N, Pujade-Lauraine E, Paule B, Paes D, Bons J (1990) Comparison of the 5-hydroxytryptamine3 (serotonin) antagonist ondansetron (GR 380332F) with high-dose metoclopramide in the control of cisplatin-induced emesis. N Engl J Med 322:816–821

    Article  CAS  Google Scholar 

  27. Pierce PA, Xie GX, Levine JD, Peroutka SJ (1996) 5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: a polymerase chain reaction study. Neuroscience 70:553–559

    Article  CAS  Google Scholar 

  28. Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, Dietrich L, Biggs D, Lafky JM, Loprinzi CL (2016) Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med 375:134–142

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark

    Jørn Herrstedt & Karin Holmskov

  2. Pulmonary Oncology Unit, University Hospital South Manchester, Manchester, UK

    Yvonne Summers & Paul D. Taylor

  3. Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

    Gedske Daugaard

  4. Department of Oncology, Herlev Hospital, Copenhagen, Denmark

    Thomas B. Christensen

  5. Acacia Pharma, Cambridge, UK

    Gabriel M. Fox

  6. School of Nursing, Midwifery and Social Work, University of Manchester, Manchester, UK

    Alexander Molassiotis

  7. School of Nursing, The Hong Kong Polytechnic University, Hung Hom, Hong Kong

    Alexander Molassiotis

Authors
  1. Jørn Herrstedt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yvonne Summers
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gedske Daugaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thomas B. Christensen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karin Holmskov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Paul D. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Gabriel M. Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexander Molassiotis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jørn Herrstedt.

Ethics declarations

The study was approved by the National Health Authorities and properly constituted Ethics Committees in Denmark and the UK and was conducted in accordance with the principles of Good Clinical Practice. All subjects gave written, informed consent. The study was registered on clintrials.gov with reference no. NCT01303978.

Conflict of interest

The study was sponsored by Acacia Pharma Ltd. The investigators had access to all data.

The journal is allowed to review the data if requested.

Jørn Herrstedt reported advisory board activity (Tesaro) and remuneration (SOBI).

Alex Molassiotis has received grants or honoraria from MSD, Merck, Helsinn, Tesaro, Norgine and Acacia Pharma.

Gabriel Fox is an employee of Acacia.

The other authors reported no conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herrstedt, J., Summers, Y., Daugaard, G. et al. Amisulpride in the prevention of nausea and vomiting induced by cisplatin-based chemotherapy: a dose-escalation study. Support Care Cancer 26, 139–145 (2018). https://doi.org/10.1007/s00520-017-3825-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-017-3825-2

Keywords

Search

Navigation