Skip to main content
Latest news
Browse specialties
Breast cancer Genitourinary cancers Lung & thoracic cancers
In focus
Next-generation sequencing: Emerging biomarkers in thyroid and NSCLCs ctDNA and bladder cancer: Current understanding and beyond ROS1 fusion-positive NSCLC NSCLC driver mutations: Discussing the importance of RET, ALK and ROS1 alterations in NSCLC Early-stage NSCLC management: Surgery, targeted treatment and immunotherapy ALK fusion-positive NSCLC: International approaches to management RET fusion-positive NSCLC: Informing on the use of pralsetinib for patients with RET fusion-positive, advanced NSCLC COVID-19 & cancer
Conferences
SABCS 2022 ESMO 2022 2022 ASCO Annual Meeting
About us
Medicine Matters Oncology
EXTENDED SEARCH
Top

01-12-2016 | Nausea and vomiting | Book chapter | Article

5. The Role of Neurokinin-1 Receptor Antagonists in CINV

Author: Bernardo Leon Rapoport, Dip. in Med., M. Med.

Publisher: Springer International Publishing

Login to get access

Abstract

Significant advances have been made in controlling chemotherapy-induced nausea and vomiting (CINV) in the past two decades. These advances are primarily due to a greater understanding of the physiological and molecular pathways underlying CINV, which resulted in major progress in the management of patients with CINV. In the early 1990s, CINV treatment included dexamethasone [1]. Improvements in the management of CINV control were achieved with the discovery of 5-hydroxytryptamine (5HT3) receptor and the development of 5HT3 receptor antagonists (RA). Additional improvements in CINV control were further made, with the usage of the combination of 5HT3 RA with dexamethasone or other corticosteroid agents at equivalent doses [2, 3].
Literature
1.
Aapro MS, Alberts DS (1981) Dexamethasone as an antiemetic in patients treated with cisplatin. N Engl J Med 305(9):520PubMed
2.
Falkson G, van Zyl AJ (1989) A phase I study of a new 5HT3-receptor antagonist, BRL43694A, an agent for the prevention of chemotherapy-induced nausea and vomiting. Cancer Chemother Pharmacol 24(3):193–196CrossRefPubMed
3.
Smith DB, Newlands ES, Spruyt OW, Begent RH, Rustin GJ, Mellor B, Bagshawe KD (1990) Ondansetron (GR38032F) plus dexamethasone: effective anti-emetic prophylaxis for patients receiving cytotoxic chemotherapy. Br J Cancer 61(2):323–324PubMedCentralCrossRefPubMed
4.
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 21:4112–4119CrossRefPubMed
5.
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 97:3090–3098CrossRefPubMed
6.
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 23:2822–2830CrossRefPubMed
7.
Rapoport BL, Jordan K, Boice JA, et al (2010) 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 18(14):428–431
8.
National Comprehensive Cancer Network. NCNN Guidelines 1.2012: Antiemesis 1.2012. 2012. Report No.: 1.2012
9.
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):v232–v243CrossRefPubMed
10.
Hesketh PJ, Bohlke K, Lyman GH, Basch E, Chesney M, Clark-Snow RA, Danso MA, Jordan K, Somerfield MR, Kris MG. Antiemetics: American Society of Clinical Oncology Focused Guideline Update. J Clin Oncol. 2015 Nov 2. pii: JCO.2015.64.3635. [Epub ahead of print]
11.
Grunberg S, Chua D, Maru A, Dinis J, DeVandry S, Boice JA, Hardwick JS, Beckford E, Taylor A, Carides A, Roila F, Herrstedt J (2011) 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 29(11):1495–1501CrossRefPubMed
12.
Arpornwirat W, Albert I, Hansen VL et al (2009) Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy. Cancer 115(24):5807–5816CrossRefPubMed
13.
Roila F, Rolski J, Ramlau R et al (2009) Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting. Ann Oncol 20(11):1867–1873CrossRefPubMed
14.
Grunberg SM, Rolski J, Strausz J et al (2009) Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol 10:549–558CrossRefPubMed
15.
Stathis M, Pietra C, Rojas C, Slusher BS (2012) Inhibition of substance P-mediated responses in NG108-15 cells by netupitant and palonosetron exhibit synergistic effects. Eur J Pharmacol 689(1-3):25–30CrossRefPubMed
16.
Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM (2012) Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol Biochem Behav 102(1):95–100CrossRefPubMed
17.
Calcagnile S, Lanzarotti C, Rossi G, Henriksson A, Kammerer KP, Timmer W (2013) 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 contraceptives. Support Care Cancer 21(10):2879–2887CrossRefPubMed
18.
Gan TJ, Gu J, Singla N, Chung F, Pearman MH, Bergese SD, Habib AS, Candiotti KA, Mo Y, Huyck S, Creed MR, Cantillon M, Rolapitant Investigation Group (2011) Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg 112(4):804–812CrossRefPubMed
19.
Poma A, Christensen J, Davis J, Kansra V, Martell RE, Hedley ML. Phase 1 positron emission tomography (PET) study of the receptor occupancy of rolapitant, a novel NK-1 receptor antagonist.J Clin Oncol 2014; 32(suppl):abstr e20690
20.
Poma A, Christensen J, Pentikis H et al (2013) Rolapitant and its major metabolite do not affect the pharmacokinetics of midazolam, a sensitive cytochrome P450 3A4 Substrate. Abstract 0441, MASCC/ISOO Symposium 2013. Support Care Cancer 21(1 Suppl)
21.
Tavorath R, Hesketh PJ (1996) Drug treatment of chemotherapy-induced delayed emesis. Drugs 52:639–648CrossRefPubMed
22.
Wilder-Smith OH, Borgeat A, Chappuis P et al (1993) Urinary serotonin metabolite excretion during cisplatin chemotherapy. Cancer 72:2239–2241CrossRefPubMed
23.
Hesketh PJ, Warr DG, Street JC et al (2011) Differential time course of action of 5-HT3 and NK1 receptor antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC). Support Care Cancer 19(9):1297–1302CrossRefPubMed
24.
Mantovani G, Maccio A, Curreli L et al (1998) Comparison of oral 5-HT3-receptor antagonists and low-dose oral metoclopramide plus I.M. dexamethasone for the prevention of delayed emesis in head and neck cancer patients receiving high-dose cisplatin. Oncol Rep 5:273–280PubMed
25.
Warr DG, Grunberg SM, Gralla RJ et al (2005) The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: pooled data from 2 randomised, double-blind, placebo controlled trials. Eur J Cancer 41:1278–1285CrossRefPubMed
26.
Martin M (1996) The severity and pattern of emesis following different cytotoxic agents. Oncology 53(Suppl 1):26–31CrossRefPubMed
27.
Lasseter KC, Gambale J, Jin B et al (2007) Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol 47:834–840CrossRefPubMed
28.
Hesketh PJ, Rossi G, Rizzi G, Palmas M, Alyasova A, Bondarenko I, Lisyanskaya A, Gralla RJ (2014) Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol 25(7):1340–1346PubMedCentralCrossRefPubMed
29.
Rapoport BL, Poma A, Hedley ML et al (2014) Phase 3 trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in subjects receiving highly emetogenic chemotherapy (HEC). J Clin Oncol 32:32
30.
Aapro M, Karthaus M, Schwartzberg LS et al (2014) Phase 3 study of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting during repeated moderately emetogenic chemotherapy cycles [abstract]. J Clin Oncol 32(Suppl 5):9502
31.
Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K, von Pawel J, Giezek H, Ahmed T, Chan CY (2006) Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol 17(6):1000–1006CrossRefPubMed
32.
Herrington JD, Jaskiewicz AD, Song J (2008) Randomized, placebo-controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer 112:2080–2087.24CrossRefPubMed
33.
Grunberg SM, Dugan M, Muss H et al (2009) Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy. Support Care Cancer 17:589–594CrossRefPubMed
34.
Van Belle SJ, Cocquyt V (2008) Fosaprepitant dimeglumine (MK-0517 or L-785,298), an intravenous neurokinin-1 antagonist for the prevention of chemotherapy induced nausea and vomiting. Expert Opin Pharmacother 9(18):3261–3270CrossRefPubMed
35.
Saito H, Yoshizawa H, Yoshimori K, Katakami N, Katsumata N, Kawahara M, Eguchi K (2013) Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann Oncol 24(4):1067–1073PubMedCentralCrossRefPubMed
36.
de Wit R, Herrstedt J, Rapoport B, Carides AD, Guoguang-Ma J, Elmer M, Schmidt C, Evans JK, Horgan KJ (2004) The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer 40(3):403–410CrossRefPubMed
37.
de Wit R, Herrstedt J, Rapoport B, Carides AD, Carides G, Elmer M, Schmidt C, Evans JK, Horgan KJ (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):4105–4111CrossRefPubMed
38.
Rapoport B, Chua D, Poma A, Arora S, Wang Y, Fein LE (2015) Study of rolapitant, a novel, long-acting, NK-1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). Support Care Cancer 23(11):3281–3288
39.
Rapoport BL, Poma A, Hedley ML, Martel RE, Navari RM (2014) Phase III trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in subjects receiving highly emetogenic chemotherapy (HEC) [abstract] J Clin Oncol 32(Suppl 5):9638. Rapoport B, Chasen M, Gridelli M, Urban L, Modiano M, Schnadig I, Poma A, Arora S, Kansra V, Schwartzberg L, Navari R Safety and efficacy assessment of rolapitant for the prevention of chemotherapy‐induced nausea and vomiting following administration of cisplatin-based highly emetogenic chemotherapy in cancer patients in two randomised Phase 3 Trials. Lancet Oncol (Manuscript in press)
40.
Schnadig ID, Modiano MR, Poma A, Hedley ML, Martel RE, Schwartzberg LS (2014) Phase III trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting (CINV) in subjects receiving moderately emetogenic chemotherapy (MEC) [abstract] J Clin Oncol 32(Suppl 5):9633. Schwartzberg L, Modiano M, Rapoport B, Chasen M, Gridelli B, Urban L, Poma A, Arora S, Navari R, Schnadig I Safety and efficacy assessment of rolapitant for the prevention of chemotherapy-induced nausea and vomiting following administration of moderately emetogenic chemotherapy in cancer patients in a randomised phase 3 trial. Lancet Oncol (Manuscript in press)
41.
Rojas C, Thomas AG, Alt J et al (2010) Palonosetron triggers 5-HT3 receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 626:193–199CrossRefPubMed
42.
Rojas C, Slusher BS (2012) Pharmacological mechanisms of 5-HT3 tachykinin NK-1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting. Eur J Pharmacol 684:1–7CrossRefPubMed
43.
Aapro M, Rugo H, Rossi G et al (2014) A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol 25:1328–1333PubMedCentralCrossRefPubMed
44.
Schwartzberg L, Aapro M, Hesketh PJ et al (2014) do NK-1 receptor antagonists contribute to nausea control. Evaluation of the novel NEPA fixed-dose combination of NK-1 receptor antagonist plus a 5-HT3 receptor antagonist from pivotal trials. Support Care Cancer 22:S107, Abstract 161
45.
US Food and Drug Administration (2014) FDA approves Akynzeo for nausea and vomiting associated with cancer chemotherapy [press release]. US Food and Drug Administration, Silver Springs, Accessed 30 Apr 2015. Available from: http://​www.​fda.​gov/​NewsEvents/​Newsroom/​PressAnnouncemen​ts
46.
Stiff PJ, Fox-Geiman MP, Kiley K et al (2013) Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant 19(1):49–55CrossRefPubMed
47.
Pielichowski W, Barzal J, Gawronski K et al (2011) A triple-drug combination to prevent nausea and vomiting following BEAM chemotherapy before autologous hematopoietic stem cell transplantation. Transplant Proc 43(8):3107–3110CrossRefPubMed
48.
Badar T, Cortes J, Borthakur G, O'Brien S, Wierda W, Garcia-Manero G, Ferrajoli A, Kadia T, Poku R, Kantarjian H, Mattiuzzi G (2015) Phase II, open label, randomized comparative trial of ondansetron alone versus the combination of ondansetron and aprepitant for the prevention of nausea and vomiting in patients with hematologic malignancies receiving regimens containing high-dose cytarabine. Biomed Res Int 2015:497597PubMedCentralCrossRefPubMed
49.
Egerer G, Eisenlohr K, Gronkowski M, Burhenne J, Riedel KD, Mikus G (2010) The NK(1) receptor antagonist aprepitant does not alter the pharmacokinetics of high-dose melphalan chemotherapy in patients with multiple myeloma. Br J Clin Pharmacol 70(6):903–907PubMedCentralCrossRefPubMed
50.
Schmitt T, Goldschmidt H, Neben K, Freiberger A, Hüsing J, Gronkowski M, Thalheimer M, le Pelzl H, Mikus G, Burhenne J, Ho AD, Egerer G (2014) Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol 32(30):3413–3420CrossRefPubMed
51.
Bechtel T, McBride A, Crawford B, Bullington S, Hofmeister CC, Benson DM Jr, Jaglowski S, Penza S, Andritsos LA, Devine SM (2014) Aprepitant for the control of delayed nausea and vomiting associated with the use of high-dose melphalan for autologous peripheral blood stem cell transplants in patients with multiple myeloma: a phase II study. Support Care Cancer 22(11):2911–2916CrossRefPubMed
52.
dos Santos LV, Souza FH, Brunetto AT, Sasse AD, da Silveira Nogueira Lima JP (2012) Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst 104(17):1280–1292CrossRefPubMed
53.
Chawla SP, Grunberg SM, Gralla RJ, Hesketh PJ, Rittenberg C, Elmer ME, Schmidt C, Taylor A, Carides AD, Evans JK, Horgan KJ (2003) Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer 97(9):2290–2300CrossRefPubMed
54.
Leal AD, Kadakia KC, Looker S, Hilger C, Sorgatz K, Anderson K, Jacobson A, Grendahl D, Seisler D, Hobday T, Loprinzi CL (2014) Fosaprepitant-induced phlebitis: a focus on patients receiving doxorubicin/cyclophosphamide therapy. Support Care Cancer 22(5):1313–1317PubMedCentralCrossRefPubMed
55.
Aapro MS, Walko CM (2010) Aprepitant: drug-drug interactions in perspective. Ann Oncol 21(12):2316–2323CrossRefPubMed
56.
Shadle CR, Lee Y, Majumdar AK, Petty KJ, Gargano C, Bradstreet TE, Evans JK, Blum RA (2004) Evaluation of potential inductive effects of aprepitant on cytochrome P450 3A4 and 2C9 activity. J Clin Pharmacol 44(3):215–223CrossRefPubMed
57.
de Jonge ME, Huitema AD, Holtkamp MJ, van Dam SM, Beijnen JH, Rodenhuis S (2005) Aprepitant inhibits cyclophosphamide bioactivation and thiotepa metabolism. Cancer Chemother Pharmacol 56(4):370–378CrossRefPubMed
58.
Rapoport BL, Weinstein C, Camacho ES, Khanani SA, Beckford-Brathwaite E, Kevill L, Vallejos W, Liang LW, Noga SJ (2015) A phase III, randomized, double-blind study of single-dose intravenous fosaprepitant in preventing chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy. J Clin Oncol 33(Suppl; abstr 9629)
59.
Albany C, Brames MJ, Fausel C, Johnson CS, Picus J, Einhorn LH (2012) Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol 30(32):3998–4003CrossRefPubMed