Abstract
Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a serotonin 5-HT3 receptor antagonist, dexamethasone and a neurokinin 1 (NK1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second-generation 5-HT3 receptor antagonist with a different half-life, a different binding capacity and a different mechanism of action than the first-generation 5-HT3 receptor antagonists appears to be the most effective agent in its class. Aprepitant, the first and only agent clinically available in the NK1 receptor antagonist drug class has been used effectively as an additive agent to the 5-HT3 receptor antagonists and dexamethasone to control CINV. Rolapitant and netupitant are other NK1 receptor antagonists that are currently in phase III clinical trials. Despite the control of emesis, nausea has not been well controlled by current agents. Olanzapine, a US-FDA approved antipsychotic, has emerged in recent trials as an effective preventative agent for CINV, as well as a very effective agent for the treatment of breakthrough emesis and nausea. Clinical trials using gabapentin, cannabinoids and ginger have not been definitive regarding their efficacy in the prevention of CINV. Additional studies are necessary for the control of nausea and for the control of CINV in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.
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References
Bloechl-Daum B, Deuson RR, Mavros P, et al. Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol. 2006;24:4472–8.
Cohen L, de Moor CA, Eisenberg P, et al. Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer. 2007;15(5):497–503.
Navari RM. Pharmacological management of chemotherapy-induced nausea and vomiting: focus on recent developments. Drugs. 2009;69:515–33.
Navari RM. Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer. Future Oncol. 2010;6:1074–84.
Curran MP, Robinson DM. Aprepitant: a review of its use in the prevention of nausea and vomiting. Drugs. 2009;69:1853–8.
Sankhala KK, Pandya DM, Sarantopoulos J, et al. Prevention of chemotherapy induced nausea and vomiting: a focus on aprepitant. Expert Opin Drug Metab Toxicol. 2009;12:1607–14.
Navari RM, Einhorn LH, Loehrer PJ, et al. A phase II trial of olanzapine, dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting. Support Care Cancer. 2007;15:1285–91.
Tan L, Liu J, Liu X, et al. Clinical research of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res. 2009;28:1–7.
Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol. 2011;9:188–95.
Navari RM. Treatment of chemotherapy-induced nausea. Community Oncol. 2012;9:20–6.
Stern RM, Koch KL, Andrews PLR, editors. Nausea: mechanisms and management. New York: Oxford University Press; 2011.
Roila F, Herrstedt J, Aapro M, et al. 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. 2010;21(5):232–43.
Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetic American Society Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29:4189–98.
NCCN Clinical Practice Guidelines in Oncology version 1 2012. Antiemesis. National Comprehensive Cancer Network (NCCN) [online]. http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. Accessed 31 July 2012.
Koga T, Fukuda H. Neurons in the nucleus of the solitary tract mediating inputs from vagal afferents and the area postrema in the pattern generator in the emetic act in dogs. Neurosci Res. 1992;14:366–79.
Yates BJ, Grelot L, Kerman IA, et al. Organization of the vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem. Am J Physiol. 1994;267:R974–83.
Navari RM. Review of updated antiemetic guidelines for chemotherapy-induced nausea and vomiting. Community Oncol. 2007;4(1 Suppl.):3S–11S.
Hesketh PJ. New treatment options for chemotherapy-induced nausea and vomiting. Support Care Cancer. 2004;12:550–4.
Navari RM. Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting: two new agents. J Support Oncol. 2003;1:89–103.
Simpson K, Spencer CM, McClellan KJ. Topisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs. 2000;59:1297–315.
Kimura E, Niimi E, Watanabe A, et al. Study on clinical effect of a continuous intravenous infusion of azasetron against nausea and vomiting induced by anticancer drugs including CDDP. Gan To Kagaku Ryoho. 1996;23:477–81.
Taguchi T, Tsukamoto F, Watanabe T, et al. Usefulness of ramosetron hydrochloride on nausea and vomiting in CMF or CEF therapy for breast cancer. Gan To Kagaku Ryoho. 1999;26:1163–70.
Hesketh PJ. Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting. Cancer Invest. 2000;18:163–73.
Navari RM, Koeller JM. Electrocardiographic and cardiovascular effects of the 5-hydroxytryptamine-3 receptor antagonists. Ann Pharmacother. 2003;37:1276–86.
World Health Organization. Dolasetron mesylate and serious cardiovascular reactions. WHO Drug Inf. 2006; 20(3):185.
U.S. Food and Drug Information. FDA drug safety communication: abnormal heart rhythms associated with use of anzemet (dolasetron mesylate) [online]. Available from URL: http://www.fda.gov/Drugs.DrugSafety/usm237081.htm [Accessed 27 Dec 2010].
Dolasetron [online]. http://www.drugs.com/fda/dolasetron. Accessed 27 Jul 2012.
Ondansetron [online]. http://www.drugs.com/fda/ondansetron. Accessed 27 July 2012.
Roila F, Warr D, Clark-Snow R, et al. Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer. 2005;13(2):104–8.
Geling O, Eichler H. 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. 2005;23:1289–94.
Hickok JT, Roscoe JA, Morrow GR, et al. 5-HT3 receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomized controlled trial. Lancet Oncol. 2005;6:765–72.
Saito M, Aogi K, Sekine I, et al. 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. 2009;10:115–24.
Warr DG, Hesketh PJ, Gralla RJ, et al. 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. 2005;23:2822–30.
Eisenberg P, MacKintosh FR, Ritch P, et al. Efficacy, safety, and pharmacokinetics of palonosetron in patients receiving highly emetogenic, cisplatin-based chemotherapy: a dose-ranging, clinical study. Ann Oncol. 2004;15:330–7.
Rojas C, Thomas AG, Alt J, et al. Palonosetron triggers 5-HT3 receptor internalization and causes prolonged inhibition of receptor function. J Pharmacol. 2010;626:193–9.
Aapro MS, Grunberg SM, Manikhas GM, et al. 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. 2006;17:1441–9.
Eisenberg P, Figueroa-Vadillo J, Zamora R, et al. 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. 2003;98:2473–82.
Gralla R, Lichinitser M, Van der Vegt S, et al. 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. 2003;14:1570–7.
Longo F, Mansueto G, Lapadula V, et al. Combination of aprepitant, palonosetron, and dexamethasone as antiemetic prophylaxis in lung cancer patients receiving multiple cycles of cisplatin-based chemotherapy. Int J Clin Pract. 2012;66(8):753–7.
Aogi K, Sakai H, Yoshizawa H, et al. A phase III open-label study to assess safety and efficacy of palonosetron for preventing chemotherapy-induced nausea and vomiting (CINV) in repeated cycles of emetogenic chemotherapy. Support Care Cancer. 2012;20(7):1507–14.
Kris MG. Why do we need another antiemetic? J Clin Oncol. 2003;21:4077–80.
Diemunsch P, Grelot L. Potential of substance P antagonists as antiemetics. Drugs. 2000;60:533–46.
Hesketh PJ, Grunberg SM, Herrstedt J, et al. 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. 2006;14:354–60.
Warr DG, Grunberg SM, Gralla RJ, et al. 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. 2005;41(9):1278–85.
Grote T, Hajdenberg J, Cartnell A, et al. Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone, and aprepitant. J Support Oncol. 2006;4(8):403–8.
Navari RM. Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. Expert Opin Investig Drugs. 2007;16:1977–85.
Lasseter KC, Gambale J, Jin B, et al. Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol. 2007;47:834–40.
Grunberg S, Chua D, Maru A, et al. Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol—EASE. J Clin Oncol. 2011;29(11):1495–501.
Navari RM. Casopitant, a neurokinin-1 receptor antagonist with anti-emetic and anti-nausea activities. Curr Opin Investig Drugs. 2008;9(7):774–85.
Grunberg SM, Rolski J, Strausz J, et al. Efficacy and safety of casopitant mesylate, a neurokinin-1 receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomized, double-blind, placebo controlled trial. Lancet Oncol. 2009;10(6):549–58.
Herrstedt J, Apornwirat W, Shaharyar A, et al. Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. J Clin Oncol. 2009;27(32):5363–9.
Hesketh PJ, Wright O, Rosati G, et al. Single-dose intravenous casopitant in combination with ondansetron and dexamethasone for the prevention of oxaliplatin-induced nausea and vomiting: a multicenter, randomized, double-blind active-controlled two arm, parallel group study. Support Care Cancer. 2012;20(7):1471–8.
Fein LE, Poma A, Hedley ML. Efficacy and safety of rolapitant, a novel NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting in subjects receiving highly emetogenic chemotherapy [abstract no. 9077]. J Clin Oncol 2012; 30 Suppl.
North Central Cancer Treatment Group. Gabapentin in preventing nausea and vomiting in patients receiving chemotherapy [ClinicalTrials.gov identifier NCT00880191]. US National Institutes of Health, ClinicalTrials.gov [online]. http://www.clinicaltrials.gov. Accessed 25 Jan 2013.
Rossi G, Tilkola SO, Rudengren C, et al. A positron emission tomography study to assess the degree of neurolinin-1 receptor occupancy in the human brain after single doses of netupitant to healthy male subjects [abstract no. 9054]. J Clin Oncol 2012; 30 Suppl.
Vardy J, Chiew KS, Gallica J, et al. Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer. 1999;94:1011–5.
Celio L, Frustaci S, Denaro A, et al. 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. 2011;19:1217–25.
Aapro M, Fabi A, Nole F, et al. 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. 2010;21:1083–8.
Bymaster FP, Calligaro D, Falcone J, et al. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996;14:87–96.
Bymaster FP, Falcone JF, Bauzon D, et al. Potent antagonism of 5-HT3 and 5-HT6 receptors by olanzapine. Eur J Pharmacol. 2001;430:341–9.
Allison DB, Casey DE. Antipsychotic-associated weight gain: a review of the literature. J Clin Psychiatry. 2001;62:22–31.
Hale AS. Olanzapine. Br J Hosp Med. 1997;58:443–5.
Goldstein LE, Sporn J, Brown S, et al. New-onset diabetes mellitus and diabetic ketoacidosis associated with olanzapine treatment. Psychosomatics. 1999;40:438–43.
Passik SD, Navari RM, Loehrer PJ, et al. A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients receiving chemotherapy. Cancer Invest. 2004;22:383–8.
Navari RM, Einhorn LH, Loehrer PJ, et al. A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting. Support Care Cancer. 2005;13:529–34.
Navari RM, Nagy CK, Gray SE. Olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Support Care Cancer 2013;21: (in press).
Irving G, Jensen M, Cramer M, et al. 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. 2009;25(3):185–92.
Guttuso T, Roscoe J, Griggs J. Effect of gabapentin on nausea induced by chemotherapy in patients with breast cancer. Lancet. 2003;361:1703–5.
Cruz FM, de Iracema Gomes Cubero D, Taranto P. Gabapentin for the prevention of chemotherapy-induced nausea and vomiting: a pilot study. Support Care Cancer. 2011; 20: 601–6.
Van Sickle MD, Duncan M, Kingsley PJ, et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science. 2005;310:329–32.
Darmani NA. Delta-9-tetrahydrocannabinol differentially suppresses cisplatin-induced emesis and indices of motor function via cannabinoid CB1 receptors in the least shrew. Pharmacol Biochem Behav. 2001;69:239–49.
Meiri E, Jhangiani H, Vredenburgh JJ, et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin. 2007;23:533–43.
Davis MP. Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opin Investig Drugs. 2008;17(1):85–95.
Mills S, Bone K, editors. Principles and practice of phytotherapy. Oxford: Churchill Livingstone; 2000.
Pillai AK, Sharma KK, Gupta YK, et al. Anti-emetic effect of ginger powder versus placebo as an add-on therapy in children and young adults receiving highly emetogenic chemotherapy. Pediatric Blood Cancer. 2011;56:234–8.
Zick SM, Ruffin MT, Normolle DP, et al. Phase II trial of encapsulated ginger as a treatment for chemotherapy-induced nausea and vomiting. Support Care Cancer. 2009;17:563–72.
Ryan JL, Heckler C, Roscoe JA, et al. Ginger reduces acute chemotherapy-induced nausea: a URCC CCOP study of 576 patients. Support Care Cancer. 2012;20(7):1479–89.
Kris MG, Hesketh PJ, Somerfield MR, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006;24:2932–47.
Rapoport BL, Jordon K, Boice JA, et al. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer. 2010;18(4):423–31.
Navari RM. Prevention of emesis from multiple-day chemotherapy regimens. J Natl Compr Canc Netw. 2007;5:51–9.
Einhorn LH, Brames ML, Dreicer R, et al. Palonosetron plus dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Support Care Cancer. 2007;15:1293–300.
Albany C, Brames ML, Fausel C, et al. Randomized, double-blind, placebo-controlled, phase III crossover study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5-HT3 antagonist plus dexamethasone in patients with germ cell tumor receiving 5-day cisplatin combination chemotherapy regimens: a Hoosier Oncology Group (HOG) study. J Clin Oncol. 2012;30:3998–4003.
Grunberg SM, Deuson R, Mavros P, et al. Incidence of chemotherapy-induced nausea and emesis after modern antiemetics: perception versus reality. Cancer. 2004;100:2261–8.
Fabi A, Barduagni M, Lauro S, et al. Is delayed chemotherapy-induced emesis well managed in oncological clinical practice? An observational study. Support Care Cancer. 2003;11:156–61.
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Navari, R.M. Management of Chemotherapy-Induced Nausea and Vomiting. Drugs 73, 249–262 (2013). https://doi.org/10.1007/s40265-013-0019-1
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DOI: https://doi.org/10.1007/s40265-013-0019-1