Treatment of Chemotherapy-Induced Nausea

  • Rudolph M. NavariEmail author


Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is perceived by patients as a major adverse effect of the treatment [1]. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of CINV [2]. Recent studies have demonstrated additional improvement in the control of CINV with the use of a number of new agents: palonosetron, a second-generation 5-HT3 receptor antagonist [3]; aprepitant, the first agent available in the drug class of neurokinin-1 (NK-1) receptor antagonists [4, 5]; recent introduction of additional NK-1 receptor antagonists netupitant and rolapitant [6, 7]; and olanzapine, an antipsychotic which blocks multiple neurotransmitters in the central nervous system [8–10].



Supported by the Reich Endowment for the Care of the Whole Patient.


  1. 1.
    Bloechl-Daum B, Deuson RR, Panagiotis M et al (2006) Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol 24:4472–4478CrossRefPubMedGoogle Scholar
  2. 2.
    Navari RM (2009) Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments. Drugs 69:515–533CrossRefPubMedGoogle Scholar
  3. 3.
    Navari RM (2010) Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer. Future Oncol 6:1073–1084CrossRefPubMedGoogle Scholar
  4. 4.
    Curran MP, Robinson DM (2009) Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs 69:1853–1858CrossRefPubMedGoogle Scholar
  5. 5.
    Sankhala KK, Pandya DM, Sarantopoulos J et al (2009) Prevention of chemotherapy induced nausea and vomiting: a focus on aprepitant. Expert Opin Drug Metab Toxicol 12:1607–1614CrossRefGoogle Scholar
  6. 6.
    Navari RM (2015) Profile of netupitant/palonosetron fixed dose combination (NEPA) and its potential in the treatment of chemotherapy-induced nausea and vomiting (CINV. Drug Des Dev Ther 9:155–161Google Scholar
  7. 7.
    Navari RM (2015) Rolapitant for the treatment of chemotherapy induced nausea and vomiting. Expert Rev Anticancer Ther 15:1127–1133CrossRefPubMedGoogle Scholar
  8. 8.
    Navari RM, Einhorn LH, Loehrer PJ et al (2005) A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. Support Care Cancer 13:529–534CrossRefPubMedGoogle Scholar
  9. 9.
    Navari RM, Einhorn LH, Loehrer PJ et al (2007) A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting. Support Care Cancer 15:1285–1291CrossRefPubMedGoogle Scholar
  10. 10.
    Tan L, Liu J, Liu X et al (2009) Clinical research of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res 28:1–7CrossRefGoogle Scholar
  11. 11.
    Stern RM, Koch KL, Andrews PLR (2011) Nausea: mechanisms and management. Oxford University Press, New YorkGoogle Scholar
  12. 12.
    Simpson K, Spencer CM, McClellan KJ (2000) Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 59:1297–1315CrossRefPubMedGoogle Scholar
  13. 13.
    Kimura E, Niimi E, Wantabe A et al (1996) Study on the clinical effect of a continuous intravenous infusion of azasetron against nausea and vomiting induced by anticancer drugs including CDDP. Gan To Kagaku Ryoho 23:477–481PubMedGoogle Scholar
  14. 14.
    Taguchi T, Tsukamoto F, Watanabe T et al (1999) Usefulness of ramosetron hydrochloride on nausea and vomiting in CMF or CEF therapy for breast cancer. Gan To Kagaku Ryoho 26:1163–1170PubMedGoogle Scholar
  15. 15.
    Dolasetron drug alert. WHO Drug Information, 40, No. 3 (2006)Google Scholar
  16. 16.
    U.S. Food and Drug Information. FDA drug safety communication: abnormal heart rhythms associated with use of Anzemet (dolasetron mesylate). Available from URL: Accessed 27 Dec 2010
  17. 17.
    Roila F, Warr D, Clark-Snow R et al (2005) Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer 13(2):104–108CrossRefPubMedGoogle Scholar
  18. 18.
    Geling O, Eichler H (2005) Should 5-Hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol 23:1289–1294CrossRefPubMedGoogle Scholar
  19. 19.
    Hickok JT, Roscoe JA, Morrow GR et al (2005) 5-HT3 receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomized controlled trial. Lancet Oncol 6:765–772PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Saito M, Aogi K, Sekine I et al (2009) Palonosetron plus dexamethasone versus granisetron plus dexamethasone for the prevention of nausea and vomiting during chemotherapy: a double-blind, double dummy, randomized, comparative phase III trial. Lancet Oncol 10:115–124CrossRefPubMedGoogle Scholar
  21. 21.
    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 23:2822–2830CrossRefPubMedGoogle Scholar
  22. 22.
    Hesketh PJ, Grunberg SM, Herrstedt J et al (2006) Combined data from two phase III trials of the NK-1 antagonist aprepitant plus a 5HT3 antagonist and a corticosteroid for prevention of chemotherapy-induced nausea and vomiting: effect of gender on treatment response. Support Care Cancer 14:354–360CrossRefPubMedGoogle Scholar
  23. 23.
    Warr DG, Grunberg SM, Gralla RJ et al (2005) The oral NK1 antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: pooled data from two randomized, double-blind, placebo controlled trials. Eur J Cancer 41:1278–1285CrossRefPubMedGoogle Scholar
  24. 24.
    Grote T, Hajdenberg Cartnell A et al (2006) Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. J Support Oncol 4:408Google Scholar
  25. 25.
    Celio L, Frustaci S, Denaro A et al (2011) Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multi-center, phase III trial. Support Care Cancer 19:1217–1225PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Aapro MS, Grunberg SM, Manikhas GM et al (2006) A phase III, double blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 17:1441–1449CrossRefPubMedGoogle Scholar
  27. 27.
    Navari RM, Gray SE, Kerr AC (2011) Olanzapine versus aprepitant for the control of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol (in press)Google Scholar
  28. 28.
    Cruz FM, de Iracema Gomes Cubero D, Taranto P (2011) Gabapentin for the prevention of chemotherapy-induced nausea and vomiting: a pilot study. Support Care Cancer (in press)Google Scholar
  29. 29.
    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 23:533–543CrossRefPubMedGoogle Scholar
  30. 30.
    Eisenberg P, MacKintosh FR, Ritch P et al (2004) Efficacy, safety, and pharmacokinetics of palonosetron in patients receiving highly emetogenic, cisplatin-based chemotherapy: a dose-ranging, clinical study. Ann Oncol 15:330–337CrossRefPubMedGoogle Scholar
  31. 31.
    Rojas C, Thomas AG, Alt J et al (2010) Palonosetron triggers 5-HT3 receptor internalization and causes prolonged inhibition of receptor function. J Pharmacol 626:193–199Google Scholar
  32. 32.
    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 5HT3 receptor antagonist: results of a phase III, single dose trial versus dolasetron. Cancer 98:2473–2482CrossRefPubMedGoogle Scholar
  33. 33.
    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 II trial comparing single dose of palonosetron with ondansetron. Ann Oncol 14:1570–1577CrossRefPubMedGoogle Scholar
  34. 34.
    Basch E, Prestrud AA, Hesketh PJ et al (2011) Antiemetic American Society Clinical Oncology clinical practice guideline update. J Clin Oncol 29:4189–4198Google Scholar
  35. 35.
    NCCN National Comprehensive Cancer Network (2015) Antiemesis: Clinical Practice Guidelines in Oncology. v 1.
  36. 36.
    Roila F, Herrstedt J, Aapro M et al (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(Suppl 5):232–243CrossRefGoogle Scholar
  37. 37.
    Navari RM (2003) Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting: two new agents. J Support Oncol 1:89–103PubMedGoogle Scholar
  38. 38.
    Vardy J, Chiew KS, Gallica J et al (1999) Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 94:1011–1015CrossRefGoogle Scholar
  39. 39.
    Aapro M, Fabi A, Nole F et al (2010) Double-blind, randomized, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol 21:1083–1088CrossRefPubMedGoogle Scholar
  40. 40.
    Bymaster FP, Calligaro D, Falcone J et al (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14:87–96CrossRefPubMedGoogle Scholar
  41. 41.
    Bymaster FP, Falcone JF, Bauzon D et al (2001) Potent antagonism of 5HT3 and 5HT6 receptors by olanzapine. Eur J Pharmacol 430:341–349CrossRefPubMedGoogle Scholar
  42. 42.
    Allison DB, Casey DE (2001) Antipsychotic-associated weight gain: a review of the literature. J Clin Psychiatry 62:22–31PubMedGoogle Scholar
  43. 43.
    Hale AS (1997) Olanzapine. Br J Hosp Med 58:443–445Google Scholar
  44. 44.
    Goldstein LE, Sporn J, Brown S et al (1999) New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics 40:438–443CrossRefPubMedGoogle Scholar
  45. 45.
    Irving G, Jensen M, Cramer M et al (2009) Efficacy and tolerability of gastric-retentive gabapentin for the treatment of post-herpetic neuralgia: results of a double-blind, randomized, placebo-controlled clinical trial. Clin J Pain 25(3):185–192CrossRefPubMedGoogle Scholar
  46. 46.
    Guttuso T, Roscoe J, Griggs J (2003) Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Lancet 361:1703–1705CrossRefPubMedGoogle Scholar
  47. 47.
    Van Sickle MD, Oland LD, Mackie K et al (2003) Delta9-tetrahydrocannabinol selectively acts on CB1 receptors in specific regions of dorsal vagal complex to inhibit emesis in ferrets. Am J Physiol Gastrointest Liver Physiol 285:G566–G576CrossRefPubMedGoogle Scholar
  48. 48.
    Darmani NA (2001) Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB1 receptors in the least shrew. Pharmacol Biochem Behav 69:239–249CrossRefPubMedGoogle Scholar
  49. 49.
    Davis MP (2008) Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opin Investig Drugs 17(1):85–95CrossRefPubMedGoogle Scholar
  50. 50.
    Mills S, Bone K (2000) Principles and practice of phytotherapy. Churchill Livingstone, OxfordGoogle Scholar
  51. 51.
    Pillai AK, Sharma KK, Gupta YK, Bakhshi S (2011) Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving high emetogenic chemotherapy. Pediatr Blood Cancer 56:234–238CrossRefPubMedGoogle Scholar
  52. 52.
    Zick SM, Ruffin MT, Normolle DP et al (2009) Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting. Support Care Cancer 17:563–572PubMedCentralCrossRefPubMedGoogle Scholar
  53. 53.
    Ryan JL, Heckler C, Dakhil SR et al (2009) Ginger for chemotherapy-related nausea in cancer patients: a URCC CCOP randomized, double-blind, placebo-controlled clinical trial of 644 cancer patients. J Clin Oncol 27(15s):abstract 9511Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Cancer Care Program, Central and South AmericaWorld Health OrganizationAtlantaUSA
  2. 2.Student Outreach ClinicIndiana University School of Medicine South BendSouth BendUSA

Personalised recommendations