Management of Acute and Delayed Chemotherapy-induced Nausea and Vomiting: Role of Netupitant-palonosetron Combination

Overview

Journal Ther Clin Risk Manag

Publisher Dove Medical Press

Date 2016 May 20

PMID 27194913

Citations 2

Authors

Piotr K Janicki

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of this review is to summarize and discuss the recently published data (both original studies and reviews) on the oral medication NEPA, consisting of netupitant (a neurokinin-1 receptor antagonist [NK1RA], 300 mg dose) and palonosetron (5-hydroxytryptamine [serotonin or 5HT] type 3 receptor antagonist [5HT3RA], 0.5 mg dose), in the prevention of the acute and delayed nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy.

Methods: This review was based on the very limited number of available published trials consisting of two Phase III studies and one Phase II dose-selecting trial.

Results: These studies demonstrated some therapeutic benefits of NEPA over related chemotherapy-induced nausea and vomiting (CINV) prophylaxis management, as well as its beneficial safety profile. In particular, compared with single-dose 0.5 mg palonosetron, the complete response rates for all phases of CINV for the first cycle of highly emetogenic chemotherapy (with cisplatin), as well as anthracycline-cyclophosphamide-based moderately emetogenic chemotherapy, were significantly higher for single-dose NEPA. The high efficacy of NEPA in terms of prevention of CINV continued throughout repeated cycles of highly and moderately emetogenic therapies.

Conclusion: It is currently recommended that patients who are administered highly emetogenic chemotherapy regimens should obtain a three-drug combination consisting of NK1RA, 5HT3RA, and dexamethasone. The recently available oral combination of NEPA plus dexamethasone provides an additional pharmacological management option that could be considered in this scenario.

Citing Articles

Arcuate Nucleus Orexin-A Signaling Alleviates Cisplatin-Induced Nausea and Vomiting Through the Paraventricular Nucleus of the Hypothalamus in Rats.

Guo F, Gao S, Xu L, Sun X, Zhang N, Gong Y Front Physiol. 2019; 9:1811.

PMID: 30618823 PMC: 6304364. DOI: 10.3389/fphys.2018.01811.

Newest Drugs for Chronic Unexplained Nausea and Vomiting.

Hasler W Curr Treat Options Gastroenterol. 2016; 14(4):371-385.

PMID: 27726068 PMC: 5814321. DOI: 10.1007/s11938-016-0110-2.

References

Gralla R, Lichinitser M, van der Vegt S, Sleeboom H, Mezger J, Peschel C . 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. 2003; 14(10):1570-7. DOI: 10.1093/annonc/mdg417. View

Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A . 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. 2003; 98(11):2473-82. DOI: 10.1002/cncr.11817. View

Aapro M, Grunberg S, Manikhas G, Olivares G, Suarez T, Tjulandin S . 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(9):1441-9. DOI: 10.1093/annonc/mdl137. View

Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H . Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009; 10(2):115-24. DOI: 10.1016/S1470-2045(08)70313-9. View

Rojas C, Thomas A, Alt J, Stathis M, Zhang J, Rubenstein E . Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol. 2009; 626(2-3):193-9. DOI: 10.1016/j.ejphar.2009.10.002. View

Haiderali A, Menditto L, Good M, Teitelbaum A, Wegner J . Impact on daily functioning and indirect/direct costs associated with chemotherapy-induced nausea and vomiting (CINV) in a U.S. population. Support Care Cancer. 2010; 19(6):843-51. DOI: 10.1007/s00520-010-0915-9. View

Navari R . Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in patients with cancer. Future Oncol. 2010; 6(7):1073-84. DOI: 10.2217/fon.10.74. View

Rojas C, Li Y, Zhang J, Stathis M, Alt J, Thomas A . The antiemetic 5-HT3 receptor antagonist Palonosetron inhibits substance P-mediated responses in vitro and in vivo. J Pharmacol Exp Ther. 2010; 335(2):362-8. PMC: 3202469. DOI: 10.1124/jpet.110.166181. View

Boccia R, Gordan L, Clark G, Howell J, Grunberg S . Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer. 2010; 19(10):1609-17. PMC: 3166600. DOI: 10.1007/s00520-010-0990-y. View

10.

Roila F, Herrstedt J, Gralla R, Tonato M . Prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: guideline update and results of the Perugia consensus conference. Support Care Cancer. 2010; 19 Suppl 1:S63-5. DOI: 10.1007/s00520-010-1044-1. View

11.

Basch E, Hesketh P, Kris M, Prestrud A, Temin S, Lyman G . Antiemetics: american society of clinical oncology clinical practice guideline update. J Oncol Pract. 2012; 7(6):395-8. PMC: 3219469. DOI: 10.1200/JOP.2011.000397. View

12.

Aapro M, Molassiotis A, Dicato M, Pelaez I, Rodriguez-Lescure A, Pastorelli D . The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012; 23(8):1986-1992. DOI: 10.1093/annonc/mds021. View

13.

Stathis M, Pietra C, Rojas C, Slusher B . Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects. Eur J Pharmacol. 2012; 689(1-3):25-30. DOI: 10.1016/j.ejphar.2012.05.037. View

14.

Rizzi A, Campi B, Camarda V, Molinari S, Cantoreggi S, Regoli D . In vitro and in vivo pharmacological characterization of the novel NK₁ receptor selective antagonist Netupitant. Peptides. 2012; 37(1):86-97. DOI: 10.1016/j.peptides.2012.06.010. View

15.

Keating G, Duggan S, Curran M . Transdermal granisetron: a guide to its use in preventing nausea and vomiting induced by chemotherapy. CNS Drugs. 2012; 26(9):787-90. DOI: 10.2165/11209440-000000000-00000. View

16.

Navari R . The current status of the use of palonosetron. Expert Opin Pharmacother. 2013; 14(10):1281-4. DOI: 10.1517/14656566.2013.799141. View

17.

Lanzarotti C, Rossi G . Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of midazolam, erythromycin, and dexamethasone. Support Care Cancer. 2013; 21(10):2783-91. DOI: 10.1007/s00520-013-1855-y. View

18.

Calcagnile S, Lanzarotti C, Rossi G, Henriksson A, Kammerer K, Timmer W . Effect of netupitant, a highly selective NK₁ receptor antagonist, on the pharmacokinetics of palonosetron and impact of the fixed dose combination of netupitant and palonosetron when coadministered with ketoconazole, rifampicin, and oral.... Support Care Cancer. 2013; 21(10):2879-87. DOI: 10.1007/s00520-013-1857-9. View

19.

Gilmore J, Peacock N, Gu A, Szabo S, Rammage M, Sharpe J . Antiemetic guideline consistency and incidence of chemotherapy-induced nausea and vomiting in US community oncology practice: INSPIRE Study. J Oncol Pract. 2013; 10(1):68-74. DOI: 10.1200/JOP.2012.000816. View

20.

Spinelli T, Calcagnile S, Giuliano C, Rossi G, Lanzarotti C, Mair S . Netupitant PET imaging and ADME studies in humans. J Clin Pharmacol. 2013; 54(1):97-108. PMC: 4282341. DOI: 10.1002/jcph.198. View