Abstract
Purpose
This review summarizes the recommendations for the prophylaxis of nausea and vomiting in adults receiving highly emetogenic chemotherapy (HEC) which includes cisplatin, mechlorethamine, streptozocin, cyclophosphamide >1500 mg/m2, carmustine, dacarbazine, and the combination of an anthracycline and cyclophosphamide (AC) administered to women with breast cancer, as agreed at the MASCC/ESMO Antiemetic Guidelines Update meeting in Copenhagen in June 2015.
Methods
A systematic review of the literature using PubMed and the Cochrane Database from 2009 to June 2015 was performed.
Results
The NK1-receptor antagonists netupitant (300 mg given in combination with palonosetron 0.5 mg as NEPA) and rolapitant have both completed phase II and III programs and were approved by FDA (both) and EMA (NEPA) in 2014–2015. Addition of one of these agents (or of (fos)aprepitant) to a combination of a serotonin (5-HT)3-receptor antagonist and dexamethasone improved the number of patients with a complete response (no emesis and no rescue medication) days 1–5 after AC HEC with 8–9 % and after non-AC HEC by 8–20 %. Olanzapine has improved control of delayed nausea as compared to aprepitant in a randomized open designed study. In the prophylaxis of delayed nausea and vomiting, metoclopramide is an option instead of aprepitant in patients receiving cisplatin-based chemotherapy and dexamethasone is an option instead of aprepitant in patients receiving AC chemotherapy.
Conclusions
Two new NK1-receptor antagonists (netupitant and rolapitant) have been included in the updated recommendations as additional options to aprepitant or fosaprepitant. Addition of one of these NK1-receptor antagonists to a combination of a 5-HT3-receptor antagonist and dexamethasone is recommended in both non-AC HEC and AC HEC. Olanzapine is included as an option in HEC in particular if nausea is the main symptom.
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References
Kris MG, Tonato M, Bria E, Ballatori E, Espersen B, Herrstedt J, Rittenberg C, Einhorn LH, Grunberg S, Saito M, Morrow G, Hesketh P (2011) Consensus recommendations for the prevention of vomiting and nausea following high-emetic-risk chemotherapy. Support Care Cancer 19(Suppl 1):S25–S32
Herrstedt J, Rapoport B, Warr D, Roila F, Bria E, Rittenberg C, Hesketh PJ (2011) Acute emesis: moderately emetogenic chemotherapy. Support Care Cancer 19(Suppl):S15–S23
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–v243
Jordan K, Chan A, Gralla RJ, Jahn F, Rapoport B, Warr D, Hesketh PJ (2016) Emetic risk classification and evaluation of the emetogenicity of antineoplastic agents. Support Care Cancer 24 (in review)
Grunberg SM, Rolski J, Strausz J, Aziz Z, Lane S, Russo MW, Wissel P, Guckert M, Wright O, Herrstedt J (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 10:549–558
Herrstedt J, Apornwirat W, Shaharyar A, Aziz Z, Roila F, Van Belle S, Russo MW, Levin J, Ranganathan S, Guckert M, Grunberg SM (2009) 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 27:5363–5369
Brygger L, Herrstedt J (2014) 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects. Expert Opin Drug Saf 13:1407–1422
Boccia RV, Gordan LN, Clark G, Howell JD, Grunberg SM, Sancuso Study Group (2011) 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 19:1609–1617
Karthaus M, Tibor C, Lorusso V et al (2015) Efficacy and safety of oral palonosetron compared with IV palonosetron administered with dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid tumors receiving cisplatin-based highly emetogenic chemotherapy (HEC). Support Care Cancer 23:2917–2923
Boccia R, Grunberg S, Franco-Gonzales E, Rubenstein E, Voisin D (2013) Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Support Care Cancer 21:1453–1460
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 29:1495–1501
Van Laere K, De Hoon J, Bormans G, Koole M, Derdelinckx I, De Lepeleire I, Declercq R, Sanabria Bohorquez SM, Hamill T, Mozley PD, Tatosian D, Xie W, Liu Y, Liu F, Zappacosta P, Mahon C, Butterfield KL, Rosen LB, Murphy MG, Hargreaves RJ, Wagner JA, Shadle CR (2012) Equivalent dynamic human brain NK1-receptor occupancy following single-dose i.v. fosaprepitant vs. oral aprepitant as assessed by PET imaging. Clin Pharmacol Ther 92:243–250
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 25:1340–1346
Rapoport B, Chua D, Poma A et al (2015) Study of rolapitant, a novel, long-acting, NK1 receptor antagonist, for the prevention of chemotherapy-induced nausea and vomiting due to highly emetogenic chemotherapy. Support Care Cancer 23:3281–3288
The Italian group for Antiemetic Research (1998) Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. J Clin Oncol 16:2937–2942
The Italian group for Antiemetic Research (2004) Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide. J Clin Oncol 22:725–729
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 randomised, multicenter, phase III trial. Support Care Cancer 19:1217–1225
Aapro M, Fabi A, Nole F et al (2010) Double-blind, randomised, 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 21:1083–1088
Celio L, Bonizzoni E, Bajetta E, Sebastiani S, Perrone T, Aapro MS (2013) Palonosetron plus single-dose dexamethasone for the prevention of nausea and vomiting in women receiving anthracycline/cyclophosphamide-containing chemotherapy: meta-analysis of individual patient data examining the effect of age on outcome in two phase III trials. Support Care Cancer 21:565–573
Raftopoulos H, Cooper W, O’Boyle E, Gabrail N, Boccia R, Gralla RJ (2015) Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial. Support Care Cancer 23:723–732
Roscoe JA, Heckler CE, Morrow GR et al (2012) Prevention of delayed nausea: a University Of Rochester Cancer Center Community Clinical Oncology Program study of patients receiving chemotherapy. J Clin Oncol 30:3389–3395
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 21:4112–4119
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 97:3090–3098
Schmoll HJ, Aapro MS, Poli-Bigelli S et al (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 17:1000–1006
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 24:1067–1073
Hu Z, Cheng Y, Zhang H, Zhou C, Han B, Zhang Y et al (2014) Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized, double-blind, placebo-controlled phase III trial. Support Care Cancer 22:979–987
Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F (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 23:2822–2830
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 18:423–431
Gralla RJ, Bosnjak SM, Hontsa A, Balser C, Rizzi G, Rossi G, Borroni ME, Jordan K (2014) A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy. Ann Oncol 25:1333–1339
Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, Sarosiek T, Oprean C, Cardona-Huerta S, Lorusso V, Karthaus M, Schwarcbrszberg L, Grunberg S (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 25:1328–1333
Rapoport B, Poma A, Hedley ML, Martell RE, Navari RM (2014) Phase 3 trial results for rolapitant, a novel NK-1 receptor antagonist, in the prevention of chemotherapy-induced nausea and vomiting in subjects receiving highly emetogenic chemotherapy. J Clin Oncol 32(suppl 5):636, A 9638
Schnadig ID, Modiano MR, Poma A, Hedley ML, Martell RE, Schwartzberg LS (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 moderately emetogenic chemotherapy (MEC). J Clin Oncol 32(suppl 5):635, A9633
Rapoport BL, Chasen MR, Gridelli C, Urban L, Modiano MR, Schnadig ID, Poma A, Arora S, Kansra V, Schwartzberg LS, Navari RM (2015) Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of cisplatin-based highly emetogenic chemotherapy in patients with cancer: two randomised, active-controlled, double-blind, phase 3 trials. Lancet Oncol 16:1079–1089
Schwartzberg LS, Modiano MR, Rapoport BL, Chasen MR, Gridelli C, Urban L, Poma A, Arora S, Navari RM, Schnadig ID (2015) Safety and efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting after administration of moderately emetogenic chemotherapy or anthracycline and cyclophosphamide regimens in patients with cancer: a randomised, active-controlled, double-blind, phase 3 trial. Lancet Oncol 16:1071–1078
Sanchez RI, Wang RW, Newton DJ, Bakhtiar R, Lu P, Chiu S-H, Evans DC, Huskey SE (2004) Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist, aprepitant. Drug Metab Dis 32:1287–1292
Majumdar AK, McCrea JB, Panebianco DL et al (2003) Effects of aprepitant on cytochrome P450 3A4 activity using midazolam as a probe. Clin Pharmacol Ther 74:150–156
Calcagnile S, Lanzarotti C, Rossi G et al (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 21:2879–2887
Natale JJ, Spinelli T, Calcagnile S, Lanzarotti C, Rossi G, Cox D, Kashef K (2015) Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: review of clinical data. J Oncol Pharm Pract. doi:10.1177/1078155215586824
Rojas C, Slusher BS (2015) Mechanisms and latest clinical studies of new NK1 receptor antagonists for chemotherapy-induced nausea and vomiting: rolapitant and NEPA (netupitant/palonosetron). Cancer Treat Rev 41(10):904–913
Sanchez RI, Wang RW, Newton DJ et al (2004) Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos 32:1287–1292
Einhorn LH, Rapoport B, Navari R, Herrstedt J, Brames MJ (2016). Antiemetic therapy for multiple-day chemotherapy, high dose chemotherapy, and breakthrough nausea and vomiting: review and consensus statements. Support Care Cancer 24.
Tan L, Liu J, Liu X et al (2009) Clinical research of olanzapine for prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res 28:131. doi:10.1186/1756-9966-28-131
Navari RM, Gray SE, Kerr AC (2011) Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol 9:188–195
Mizukami N, Yamanchi M, Koike K et al (2014) Olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving highly or moderately emetogenic chemotherapy: a randomized, double-blind, placebo-controlled study. J Pain Symptom Manag 47:542–550
Navari RM, Nagy CK (2015). Olanzapine versus fosaprepitant for the prevention of nausea and vomiting in patients receiving concurrent chemoradiation treatment. J Clin Oncol 33: (suppl; abstr 9502).
Abe M, Hirashima Y, Kasamatsu Y et al (2016) Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial. Support Care Cancer 24:675–682
Navari RM, Qin R, Ruddy KJ et al (2015) Olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC): alliance A221301, a randomized, double-blind, placebo-controlled trial. J Clin Oncol 33(suppl 29S):abstract 176
Roila F, Ruggeri B, Ballatori E et al (2015) Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol 26:1248–1253
Roila F, Ruggeri B, Ballatori E, Del Favero A, Tonato M (2013) Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol 32:101–106
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Jørn Herrstedt: Consultant Tesaro and remuneration SOBI.
Fausto Roila: No conflict of interest.
David Warr: Consultant Helsinn, Merck, Tesaro.
Luigi Celio: Consultant Helsinn.
Rudolp M Navari: Consultant Tesaro.
Paul J Hesketh: No conflict of interest.
Alexandre Chan: Consultant and remuneration MSD.
Matti S Aapro: Consultant Helsinn, Merck/MSD, Tesaro, remuneration Helsinn, Tesaro, Roche, Esai, Merk/MSD and funding Helsinn.
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Herrstedt, J., Roila, F., Warr, D. et al. 2016 Updated MASCC/ESMO Consensus Recommendations: Prevention of Nausea and Vomiting Following High Emetic Risk Chemotherapy. Support Care Cancer 25, 277–288 (2017). https://doi.org/10.1007/s00520-016-3313-0
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DOI: https://doi.org/10.1007/s00520-016-3313-0