The nature of nausea: prevalence, etiology, and treatment in patients with advanced cancer not receiving antineoplastic treatment

  • Signe HarderEmail author
  • Jørn Herrstedt
  • Jesper Isaksen
  • Mette Asbjoern Neergaard
  • Karin Frandsen
  • Jarl Sigaard
  • Lise Mondrup
  • Bodil Abild Jespersen
  • Mogens Groenvold
Original Article



The prevalence of nausea/vomiting in patients with advanced cancer has a wide range. Due to a very low level of evidence regarding antiemetic treatment, current guidelines recommend an etiology-based approach. The evidence for this approach is also slim and research is urgently needed.


(Part One) to elucidate the prevalence of nausea and the possible associations with sociodemographic and clinical variables and (Part Two) to investigate possible etiologies of nausea and antiemetic treatments initiated in patients with nausea.


Patients with advanced cancer and no recent antineoplastic treatment were included in a prospective two-part study. In Part One, patients completed an extended version of the EORTC QLQ-C15-PAL. Nauseated patients could then be included in Part Two in which possible etiologies and antiemetic treatment were recorded and a follow-up questionnaire was completed.


Eight hundred twenty-one patients were included and 46% reported any degree of nausea. Younger age and female sex were associated with a higher degree of nausea. Common etiologies included constipation, opioid use, and “other,” and treatments associated with a statistically significant decrease in nausea/vomiting were olanzapine, laxatives, corticosteroids, domperidone, and metoclopramide.


Nausea was a common symptom in this patient population and many different etiologies were suggested. Most patients reported a lower degree of nausea at follow-up. More research in treatment approaches and specific antiemetics is strongly needed.


Nausea Advanced cancer N/V Etiology Treatment 



Funding was obtained from The Danish Cancer Society, the IMK foundation, and the Region of Southern Denmark. The funding sources had no influence on design, conduction, analyses of results, or manuscript writing.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Seow H, Barbera L, Sutradhar R, Howell D, Dudgeon D, Atzema C, Liu Y, Husain A, Sussman J, Earle C (2011) Trajectory of performance status and symptom scores for patients with cancer during the last six months of life. J Clin Oncol 29(9):1151–1158CrossRefGoogle Scholar
  2. 2.
    Kirkova J, Rybicki L, Walsh D, Aktas A (2012) Symptom prevalence in advanced cancer: age, gender, and performance status interactions. Am J Hosp Palliat Care 29(2):139–145CrossRefGoogle Scholar
  3. 3.
    Gupta M, Sahi MS, Bhargava A, Talwar V (2016) A prospective evaluation of symptom prevalence and overall symptom burden among cohort of critically ill cancer patients. Indian J Palliat Care 22(2):118–124CrossRefGoogle Scholar
  4. 4.
    Laugsand EA, Sprangers MA, Bjordal K, Skorpen F, Kaasa S, Klepstad P (2010) Health care providers underestimate symptom intensities of cancer patients: a multicenter European study. Health Qual Life Outcomes 8:104CrossRefGoogle Scholar
  5. 5.
    Sigurdardottir KR, Haugen DF (2008) Prevalence of distressing symptoms in hospitalised patients on medical wards: a cross-sectional study. BMC Palliat Care 7:16CrossRefGoogle Scholar
  6. 6.
    Fainsinger R, Miller MJ, Bruera E, Hanson J, Maceachern T (1991) Symptom control during the last week of life on a palliative care unit. J Palliat Care 7(1):5–11PubMedGoogle Scholar
  7. 7.
    Delgado-Guay MO, Rodriguez-Nunez A, Shin SH, Chisholm G, Williams J, Frisbee-Hume S, Bruera E (2016) Characteristics and outcomes of patients with advanced cancer evaluated by a palliative care team at an emergency center. A retrospective study. Support Care Cancer 24(5):2287–2295CrossRefGoogle Scholar
  8. 8.
    Jimenez A, Madero R, Alonso A, Martinez-Marin V, Vilches Y, Martinez B et al (2011) Symptom clusters in advanced cancer. J Pain Symptom Manag 42(1):24–31CrossRefGoogle Scholar
  9. 9.
    Vainio A, Auvinen A (1996) Prevalence of symptoms among patients with advanced cancer: an international collaborative study. Symptom Prevalence Group. J Pain Symptom Manag 12(1):3–10CrossRefGoogle Scholar
  10. 10.
    Harder SL, Groenvold M, Herrstedt J, Johnsen AT (2019) Nausea in advanced cancer: relationships between intensity, burden, and the need for help. Support Care Cancer 27(1):265–273Google Scholar
  11. 11.
    Walsh D, Donnelly S, Rybicki L (2000) The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients. Support Care Cancer 8(3):175–179CrossRefGoogle Scholar
  12. 12.
    Walsh D, Davis M, Ripamonti C, Bruera E, Davies A, Molassiotis A (2017) 2016 updated MASCC/ESMO consensus recommendations: management of nausea and vomiting in advanced cancer. Support Care Cancer 25(1):333–340CrossRefGoogle Scholar
  13. 13.
    Glare P, Miller J, Nikolova T, Tickoo R (2011) Treating nausea and vomiting in palliative care: a review. Clin Interv Aging 6:243–259CrossRefGoogle Scholar
  14. 14.
    Groenvold M, Petersen MA, Aaronson NK, Arraras JI, Blazeby JM, Bottomley A, Fayers PM, de Graeff A, Hammerlid E, Kaasa S, Sprangers MA, Bjorner JB, EORTC Quality of Life Group (2006) The development of the EORTC QLQ-C15-PAL: a shortened questionnaire for cancer patients in palliative care. Eur J Cancer 42(1):55–64CrossRefGoogle Scholar
  15. 15.
    Petersen MA, Aaronson NK, Arraras JI, Chie WC, Conroy T, Costantini A, Dirven L, Fayers P, Gamper EM, Giesinger JM, Habets EJJ, Hammerlid E, Helbostad J, Hjermstad MJ, Holzner B, Johnson C, Kemmler G, King MT, Kaasa S, Loge JH, Reijneveld JC, Singer S, Taphoorn MJB, Thamsborg LH, Tomaszewski KA, Velikova G, Verdonck-de Leeuw IM, Young T, Groenvold M, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (2018) The EORTC CAT Core-the computer adaptive version of the EORTC QLQ-C30 questionnaire. Eur J Cancer 100:8–16CrossRefGoogle Scholar
  16. 16.
    Fayers PM, Aaronson N, Bjordal K, Groenvold M, Curran D, Bottomley A (2001) The EORTC QLQ-C30 scoring manual, 3rd edn. European organisation for research and treatment of cancer, BrusselsGoogle Scholar
  17. 17.
    Groenvold M, Petersen MA (2006) Addendum to the EORTC QLQ-C30 scoring manual: scoring of the EORTC QLQ-C15-PAL. European organisation for research and treatment of cancer, BrusselsGoogle Scholar
  18. 18.
    Potter J, Hami F, Bryan T, Quigley C (2003) Symptoms in 400 patients referred to palliative care services: prevalence and patterns. Palliat Med 17(4):310–314CrossRefGoogle Scholar
  19. 19.
    Addington-Hall J, McCarthy M (1995) Dying from cancer: results of a national population-based investigation. Palliat Med 9(4):295–305CrossRefGoogle Scholar
  20. 20.
    Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Kiyasu E, Sobel K, Coyle N, Kemeny N, Norton L (1994) The memorial symptom assessment scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 30a(9):1326–1336CrossRefGoogle Scholar
  21. 21.
    Conill C, Verger E, Henriquez I, Saiz N, Espier M, Lugo F et al (1997) Symptom prevalence in the last week of life. J Pain Symptom Manag 14(6):328–331CrossRefGoogle Scholar
  22. 22.
    Cheung WY, Le LW, Gagliese L, Zimmermann C (2011) Age and gender differences in symptom intensity and symptom clusters among patients with metastatic cancer. Support Care Cancer 19(3):417–423CrossRefGoogle Scholar
  23. 23.
    Sekine I, Segawa Y, Kubota K, Saeki T (2013) Risk factors of chemotherapy-induced nausea and vomiting: index for personalized antiemetic prophylaxis. Cancer Sci 104(6):711–717CrossRefGoogle Scholar
  24. 24.
    Jordhoy MS, Fayers P, Loge JH, Saltnes T, Ahlner-Elmqvist M, Kaasa S (2001) Quality of life in advanced cancer patients: the impact of sociodemographic and medical characteristics. Br J Cancer 85(10):1478–1485CrossRefGoogle Scholar
  25. 25.
    Dong ST, Butow PN, Costa DS, Lovell MR, Agar M (2014) Symptom clusters in patients with advanced cancer: a systematic review of observational studies. J Pain Symptom Manag 48(3):411–450CrossRefGoogle Scholar
  26. 26.
    Johnsen AT, Petersen MA, Pedersen L, Groenvold M (2009) Symptoms and problems in a nationally representative sample of advanced cancer patients. Palliat Med 23(6):491–501CrossRefGoogle Scholar
  27. 27.
    Jarlbaek L, Hansen DG, Bruera E, Andersen M (2010) Frequency of opioid use in a population of cancer patients during the trajectory of the disease. Clin Oncol (R Coll Radiol) 22(3):199–207CrossRefGoogle Scholar
  28. 28.
    Kane-Gill SL, Rubin EC, Smithburger PL, Buckley MS, Dasta JF (2014) The cost of opioid-related adverse drug events. J Pain Palliat Care Pharmacother 28(3):282–293CrossRefGoogle Scholar
  29. 29.
    Stephenson J, Davies A (2006) An assessment of aetiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer. Support Care Cancer 14(4):348–353CrossRefGoogle Scholar
  30. 30.
    Bentley A, Boyd K (2001) Use of clinical pictures in the management of nausea and vomiting: a prospective audit. Palliat Med 15(3):247–253CrossRefGoogle Scholar
  31. 31.
    To TH, Agar M, Yates P, Currow DC (2014) Prescribing for nausea in palliative care: a cross-sectional national survey of Australian palliative medicine doctors. J Palliat Med 17(9):1032–1036CrossRefGoogle Scholar
  32. 32.
    Nauck F, Ostgathe C, Klaschik E, Bausewein C, Fuchs M, Lindena G, Neuwöhner K, Schulenberg D, Radbruch L, Working Group on the Core Documentation for Palliative Care Units in Germany (2004) Drugs in palliative care: results from a representative survey in Germany. Palliat Med 18(2):100–107CrossRefGoogle Scholar
  33. 33.
    Lindqvist O, Lundquist G, Dickman A, Bukki J, Lunder U, Hagelin CL et al (2013) Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion. J Palliat Med 16(1):38–43CrossRefGoogle Scholar
  34. 34.
    Berger MJ, Ettinger DS, Aston J, Barbour S, Bergsbaken J, Bierman PJ, Brandt D, Dolan DE, Ellis G, Kim EJ, Kirkegaard S, Kloth DD, Lagman R, Lim D, Loprinzi C, Ma CX, Maurer V, Michaud LB, Nabell LM, Noonan K, Roeland E, Rugo HS, Schwartzberg LS, Scullion B, Timoney J, Todaro B, Urba SG, Shead DA, Hughes M (2017) NCCN guidelines insights: antiemesis, version 2.2017. J Natl Compr Cancer Netw 15(7):883–893CrossRefGoogle Scholar
  35. 35.
    Herrstedt J, Roila F, Warr D, Celio L, Navari RM, Hesketh PJ, Chan A, Aapro MS (2017) 2016 updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high emetic risk chemotherapy. Support Care Cancer 25(1):277–288CrossRefGoogle Scholar
  36. 36.
    Available from: Accessed Sep 2018
  37. 37.
    Leelakanok N, Holcombe A, Schweizer ML (2016) Domperidone and risk of ventricular arrhythmia and cardiac death: a systematic review and meta-analysis. Clin Drug Investig 36(2):97–107CrossRefGoogle Scholar
  38. 38.
    Hui D, Glitza I, Chisholm G, Yennu S, Bruera E (2013) Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials. Cancer 119(5):1098–1105CrossRefGoogle Scholar
  39. 39.
    Hardy JR, O'Shea A, White C, Gilshenan K, Welch L, Douglas C (2010) The efficacy of haloperidol in the management of nausea and vomiting in patients with cancer. J Pain Symptom Manag 40(1):111–116CrossRefGoogle Scholar
  40. 40.
    Sinnott C (2002) Problems recruiting cancer patients to a comparative clinical trial of drug treatments for neuropathic pain in palliative care. J Pain Symptom Manag 23(4):270–272CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Signe Harder
    • 1
    • 2
    • 3
    Email author
  • Jørn Herrstedt
    • 4
    • 5
  • Jesper Isaksen
    • 6
  • Mette Asbjoern Neergaard
    • 7
  • Karin Frandsen
    • 8
  • Jarl Sigaard
    • 9
  • Lise Mondrup
    • 9
  • Bodil Abild Jespersen
    • 7
  • Mogens Groenvold
    • 8
    • 10
  1. 1.Department of OncologyOdense University HospitalOdense CDenmark
  2. 2.Institute of Clinical ResearchUniversity of Southern DenmarkOdenseDenmark
  3. 3.OPEN, Odense Patient data Explorative NetworkOdense University HospitalOdenseDenmark
  4. 4.Department of Clinical OncologyZealand University HospitalRoskildeDenmark
  5. 5.Faculty of Health and Medical SciencesCopenhagen UniversityCopenhagenDenmark
  6. 6.Palliative Team, Department of OncologyOdense University HospitalOdense CDenmark
  7. 7.Palliative Care team, Department of OncologyAarhus University HospitalAarhusDenmark
  8. 8.The Research Unit, Department of Palliative MedicineBispebjerg and Frederiksberg HospitalsCopenhagenDenmark
  9. 9.The Palliative Care TeamHospital of Southwest JutlandEsbjergDenmark
  10. 10.Department of Public HealthUniversity of CopenhagenCopenhagenDenmark

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