Nausea and Vomiting

  • Tara L. Lin*
  • David S. Ettinger
Part of the Cancer Drug Discovery and Development book series (CDD&D)


Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for many cancer patients despite recent advances in pharmacologic therapy (Grunberg et al. Cancer 2004;100(10):2261–8). In addition to significant physical consequences including dehydration, nutritional compromise, and metabolic alterations, it may have a dramatic impact on a patient’s quality of life (Mitchell EP Semin Oncol 1992;19(5):566–79). Despite the dissemination of detailed guidelines for preventive antiemetic regimens, some patients continue to receive suboptimal prophylaxis against CINV. Symptoms of nausea and vomiting after chemotherapy are often more difficult to manage than if the symptoms had been prevented initially with appropriate pharmacologic intervention. Notably, some patients actually develop a psychological component to their nausea and vomiting as a result of inadequate management in the past. The pathophysiology of CINV, principles of antiemetic prophylaxis, the emetogenic potential of common chemotherapeutics, classes of antiemetic therapy, and guidelines for prevention and acute management of CINV will be discussed.


Chemotherapy side effects Nausea Antiemetics Emesis 


  1. 1.
    Grunberg SM, Deuson RR, Mavros P,et al. 2004; . Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100:(10)2261–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Mitchell EP. 1992; Gastrointestinal toxicity of chemotherapeutic agents. Semin Oncol 19:(5)566–79.PubMedGoogle Scholar
  3. 3.
    Morran C, Smith DC, Anderson DA, McArdle CS. 1979; Incidence of nausea and vomiting with cytotoxic chemotherapy: a prospective randomised trial of antiemetics. Br Med J 1:(6174)1323–4.PubMedCrossRefGoogle Scholar
  4. 4.
    Coates A, Abraham S, Kaye SB,. et al. 1983; On the receiving end – patient perception of the side-effects of cancer chemotherapy. Eur J Cancer Clin Oncol 19:(2)203–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Lindley C, McCune JS, Thomason TE,. et al. 1999; Perception of chemotherapy side effects cancer versus noncancer patients. Cancer Pract 7:(2)59–65.PubMedCrossRefGoogle Scholar
  6. 6.
    de Boer-Dennert M, de Wit R, Schmitz PI,. et al. 1997; Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer 76:(8)1055–61.PubMedCrossRefGoogle Scholar
  7. 7.
    Borison HL, Wang SC. 1953; Physiology and pharmacology of vomiting. Pharmacol Rev 5:(2)193–230.PubMedGoogle Scholar
  8. 8.
    Miller AD, Leslie RA. 1994; The area postrema and vomiting. Front Neuroendocrinol 15:(4)301–20.PubMedCrossRefGoogle Scholar
  9. 9.
    Carpenter DO. 1990; Neural mechanisms of emesis. Can J Physiol Pharmacol 68:(2)230–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Dodds LJ. 1985; The control of cancer chemotherapy-induced nausea and vomiting. J Clin Hosp Pharm 10:(2)143–66.PubMedGoogle Scholar
  11. 11.
    Saito R, Takano Y, Kamiya HO. 2003; Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. J Pharmacol Sci 91:(2)87–94.PubMedCrossRefGoogle Scholar
  12. 12.
    de Wit R, Herrstedt J, Rapoport B,. et al. 2003; Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 21:(22)4105–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Poli-Bigelli S, Rodrigues-Pereira J, Carides AD,. et al. 2003; Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer 97:(12)3090–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Hesketh PJ, Grunberg SM, Gralla RJ,. et al. 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:(22)4112–19.PubMedCrossRefGoogle Scholar
  15. 15.
    Warr DG, Hesketh PJ, Gralla RJ,. et al. 2005; Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23:(12)2822–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Moher D, Arthur AZ, Pater JL. 1984; Anticipatory nausea and/or vomiting. Cancer Treat Rev 11:(3)257–64.PubMedCrossRefGoogle Scholar
  17. 17.
    Pollera CF, Giannarelli D. 1989; Prognostic factors influencing cisplatin-induced emesis Definition and validation of a predictive logistic model. Cancer 64:(5)1117–22.PubMedCrossRefGoogle Scholar
  18. 18.
    Hesketh PJ, Kris MG, Grunberg SM,. et al. 1997; Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 15:(1)103–9.PubMedGoogle Scholar
  19. 19.
    Koeller JM, Aapro MS, Gralla RJ,. et al. 2002; Antiemetic guidelines: creating a more practical treatment approach. Support Care Cancer 10:(7)519–22.PubMedCrossRefGoogle Scholar
  20. 20.
    Mitchelson F. 1992; Pharmacological agents affecting emesis A review (Part I). Drugs 43:(3)295–315.PubMedCrossRefGoogle Scholar
  21. 21.
    Bountra C, Gale JD, Gardner CJ,. et al. 1996; Towards understanding the aetiology and pathophysiology of the emetic reflex: novel approaches to antiemetic drugs. Oncology 53:(Suppl 1)102–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Chevallier B, Cappelaere P, Splinter T,. et al. 1997; A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy. Support Care Cancer 5:(1)22–30.PubMedCrossRefGoogle Scholar
  23. 23.
    Warr D, Wilan A, Venner P,. et al. 1992; A randomised, double-blind comparison of granisetron with high-dose metoclopramide, dexamethasone and diphenhydramine for cisplatin-induced emesis An NCI Canada Clinical Trials Group Phase III Trial. Eur J Cancer 29A:(1)33–6.PubMedGoogle Scholar
  24. 24.
    Heron JF, Goedhals L, Jordaan JP, Cunningham J, Cedar E. 1994; Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin-induced emesis The Granisetron Study Group. Ann Oncol 5:(7)579–84.PubMedGoogle Scholar
  25. 25.
    Bonneterre J, Hecquet B. 1995; Granisetron (IV) compared with ondansetron (IV plus oral) in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy A cross-over study. Bull Cancer 82:(12)1038–43.PubMedGoogle Scholar
  26. 26.
    Stewart A, McQuade B, Cronje JD,. et al. 1995; Ondansetron compared with granisetron in the prophylaxis of cyclophosphamide-induced emesis in out-patients: a multicentre, double-blind, double-dummy, randomised, parallel-group study Emesis Study Group for Ondansetron and Granisetron in Breast Cancer Patients. Oncology 52:(3)202–10.PubMedCrossRefGoogle Scholar
  27. 27.
    Martoni A, Angelelli B, Guaraldi M, Strocchi E, Pannuti F. 1996; An open randomised cross-over study on granisetron versus ondansetron in the prevention of acute emesis induced by moderate dose cisplatin-containing regimens. Eur J Cancer 32A:(1)82–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Hesketh P, Navari R, Grote T,. et al. 1996; Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in patients with cancer Dolasetron Comparative Chemotherapy-induced Emesis Prevention Group. J Clin Oncol 14:(8)2242–9.PubMedGoogle Scholar
  29. 29.
    Audhuy B, Cappelaere P, Martin M,. et al. 1996; A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy. Eur J Cancer 32A:(5)807–13.PubMedGoogle Scholar
  30. 30.
    Lofters WS, Pater JL, Zee B,. et al. 1997; Phase III double-blind comparison of dolasetron mesylate and ondansetron and an evaluation of the additive role of dexamethasone in the prevention of acute and delayed nausea and vomiting due to moderately emetogenic chemotherapy. J Clin Oncol 15:(8)2966–73.PubMedGoogle Scholar
  31. 31.
    Seynaeve C, Schuller J, Buser K,et al. 1992; Comparison of the anti-emetic efficacy of different doses of ondansetron, given as either a continuous infusion or a single intravenous dose, in acute cisplatin-induced emesis A multicentre, double-blind, randomised, parallel group study. Ondansetron Study Group.Br J Cancer66:(1)192–7.PubMedCrossRefGoogle Scholar
  32. 32.
    Ettinger DS, Eisenberg PD, Fitts D, Friedman C, Wilson-Lynch K, Yocom K. 1996; A double-blind comparison of the efficacy of two dose regimens of oral granisetron in preventing acute emesis in patients receiving moderately emetogenic chemotherapy. Cancer 78:(1)144–51.PubMedCrossRefGoogle Scholar
  33. 33.
    Harman GS, Omura GA, Ryan K, Hainsworth JD, Cramer MB, Hahne WF. 1996; A randomized, double-blind comparison of single-dose and divided multiple-dose dolasetron for cisplatin-induced emesis. Cancer Chemother Pharmacol 38:(4)323–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Perez EA, Hesketh P, Sandbach J,. et al. 1998; Comparison of single-dose oral granisetron versus intravenous ondansetron in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy: a multicenter, double-blind, randomized parallel study. J Clin Oncol 16:(2)754–60.PubMedGoogle Scholar
  35. 35.
    Gralla RJ, Navari RM, Hesketh PJ,. et al. 1998; Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin-based chemotherapy. J Clin Oncol 16:(4)1568–73.PubMedGoogle Scholar
  36. 36.
    Eisenberg P, Figueroa-Vadillo J, Zamora R,. et al. 2003; Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 98:(11)2473–82.PubMedCrossRefGoogle Scholar
  37. 37.
    Gralla R, Lichinitser M, Van Der Vegt S,. et al. 2003; Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 14:(10)1570–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Moertel CG, Reitemeier RJ, Gage RP. 1963; A controlled clinical evaluation of antiemetic drugs. JAMA 186:116–18.PubMedCrossRefGoogle Scholar
  39. 39.
    Kris MG, Gralla RJ, Tyson LB,. et al. 1985; Improved control of cisplatin-induced emesis with high-dose metoclopramide and with combinations of metoclopramide, dexamethasone, and diphenhydramine Results of consecutive trials in 255 patients. Cancer 55:(3)527–34.PubMedCrossRefGoogle Scholar
  40. 40.
    Ioannidis JP, Hesketh PJ, Lau J. 2000; Contribution of dexamethasone to control of chemotherapy-induced nausea and vomiting: a meta-analysis of randomized evidence. J Clin Oncol 18:(19)3409–22.PubMedGoogle Scholar
  41. 41.
    <bib id="bib41_10"> <no>41</no> <x>. </x> <title type="contributor">Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer The Italian Group for Antiemetic Research</title> <x>. </x> <title type="journal">N Engl J Med</title> <x> </x> <date>1995</date> <x>;</x> <vol>332</vol> <issue>(1)</issue> <x>:</x> <page type="first">1</page> <x>&#x2013;</x> <page type="last">5</page> <x>.</x> </bib> Google Scholar
  42. 42.
    Shadle CR, Lee Y, Majumdar AK,. et al. 2004; Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol 44:(3)215–23.PubMedCrossRefGoogle Scholar
  43. 43.
    Razavi D, Delvaux N, Farvacques C,. et al. 1993; Prevention of adjustment disorders and anticipatory nausea secondary to adjuvant chemotherapy: a double-blind, placebo-controlled study assessing the usefulness of alprazolam. J Clin Oncol 11:(7)1384–90.PubMedGoogle Scholar
  44. 44.
    Sallan SE, Zinberg NE, Frei E, 3rd. 1975; Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy. N Engl J Med 293:(16)795–7.PubMedCrossRefGoogle Scholar
  45. 45.
    Tramer MR, Carroll D, Campbell FA, Reynolds DJ, Moore RA, McQuay HJ. 2001; Cannabinoids for control of chemotherapy-induced nausea and vomiting: quantitative systematic review. BMJ 323:(7303)16–21.PubMedCrossRefGoogle Scholar
  46. 46.
    Meiri E, Jhangiani H, Vredenburgh JJ,. et al. 2007; Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 23:(3)533–43.PubMedCrossRefGoogle Scholar
  47. 47.
    Morrow GR, Morrell C. 1982; Behavioral treatment for the anticipatory nausea and vomiting induced by cancer chemotherapy. N Engl J Med 307:(24)1476–80.PubMedCrossRefGoogle Scholar
  48. 48.
    Redd WH, Andrykowski MA. 1982; Behavioral intervention in cancer treatment: controlling aversion reactions to chemotherapy. J Consult Clin Psychol 50:(6)1018–29.PubMedCrossRefGoogle Scholar
  49. 49.
    Horiot JC. 2004; Prophylaxis versus treatment: is there a better way to manage radiotherapy-induced nausea and vomiting? Int J Radiat Oncol Biol Phys 60:(4)1018–25.PubMedCrossRefGoogle Scholar
  50. 50.
    Franzen L, Nyman J, Hagberg H,. et al. 1996; A randomised placebo controlled study with ondansetron in patients undergoing fractionated radiotherapy. Ann Oncol 7:(6)587–92.PubMedGoogle Scholar
  51. 51.
    Okamoto S, Takahashi S, Tanosaki R,. et al. 1996; Granisetron in the prevention of vomiting induced by conditioning for stem cell transplantation: a prospective randomized study. Bone Marrow Transplant 17:(5)679–83.PubMedGoogle Scholar
  52. 52.
    Priestman TJ, Roberts JT, Upadhyaya BK. 1993; A prospective randomized double-blind trial comparing ondansetron versus prochlorperazine for the prevention of nausea and vomiting in patients undergoing fractionated radiotherapy. Clin Oncol (R Coll Radiol) 5:(6)358–63.CrossRefGoogle Scholar
  53. 53.
    Feyer P, Maranzano E, Molassiotis A,. et al. 2005; Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines. Support Care Cancer 13:(2)122–8.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press, a part of Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Tara L. Lin*
    • 1
  • David S. Ettinger
    • 1
  1. 1.David Geffen School of Medicine at UCLA10833 Le Conte AvenueCAUSA

Personalised recommendations