Prevention of Nausea and Vomiting in Oncology

Background & Aims. Despite significant progress achieved over last 25 years, nausea and especially vomiting remain basic side effects of chemotherapy affecting patients’ quality of life. Modern antiemetic therapy permits to reduce the frequency of acute vomiting to 20–30 %, whereas the effectiveness of nausea prevention is higher. Available domestic publications do not describe fundamentals of the antiemetic therapy during treatment with cytostatic agents. The objective of this study is to evaluate the effectiveness of itopride in combined antiemetic therapy for prevention of acute nausea and vomiting, as well as in single drug therapy for arresting delayed vomiting.

Methods. 30 patients were enrolled in the study (breast cancer — 10 patients, ovarian cancer — 8 patients, gastric cancer — 2 patients, colorectal cancer — 5 patients, and lung cancer — 5 patients): 25 women and 5 men aged from 40 to 70 years. All patients received chemotherapy earlier, which had unfavorable effects on the tolerability of subsequent therapy. All patients underwent chemotherapy with different degrees of emetogenicity during the study.

Results. The study has demonstrated that overall effectiveness of a combination of itopride with 5-HT₃ receptor antagonists for prevention of acute vomiting was equal to 100 %. Overall effectiveness of itopride for prevention of delayed vomiting was equal to 80 %.

Conclusion. The combination of itopride with 5-HT₃ receptor antagonists can be recommended for prevention of delayed vomiting in moderately emetogenic chemotherapeutic regimens.

• Anton Vladimirovich Snegovoi N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478
• V.B. Larionova N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478
• I.B. Kononenko N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478
• L.V. Manzyuk N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478
• A.I. Saltanov N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478
• V.Yu. Sel’chuk N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478 ; ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское шоссе, д. 24, Москва, Российская Федерация, 115478

1. Scotte F. The Importance of Supportive Care in Optimizing Treatment Outcomes of Patients with Advanced Prostate Cancer. The Oncologist. 2012;17(Suppl. 1):23–30. doi: 10.1634/theoncologist.2012-s1-23. DOI: https://doi.org/10.1634/theoncologist.2012-S1-23
2. Warr D. Chemotherapy- and cancer-related nausea and vomiting. Curr Oncol. 2008;15(Suppl. 1):S4–9. doi: 10.3747/co.2008.171. DOI: https://doi.org/10.3747/co.2008.171
3. Rolia 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;5:v232–43. doi: 10.1093/annonc/mdq194. DOI: https://doi.org/10.1093/annonc/mdq194
4. Rojas C, Slusher BS. Pharmacological mechanisms of 5-HT3 and tachykinin NK1 receptor antagonism to prevent chemotherapy-induced nausea and vomiting. Eur J Pharmacol. 2012;684:1–7. doi: 10.1016/j.ejphar.2012.01.046. DOI: https://doi.org/10.1016/j.ejphar.2012.01.046
5. Herrstedt J. Antiemetics: an update and the MASCC guidelines applied in clinical practice. J Nat Clin Pract Oncol. 2008;5(1):32–43. doi: 10.1038/ncponc1021. DOI: https://doi.org/10.1038/ncponc1021
6. Pater JL, Lofters WS, Zee B, et al. The role of the 5-HT3 antagonists ondansetron and dolasetron in the control of delayed onset nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Ann Oncol. 1997;8:181–5. DOI: https://doi.org/10.1023/A:1008247830641
7. The Italian Group for Antiemetic Research. Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. N Engl J Med. 1995;332:1–5. doi: 10.1056/nejm199501053320101. DOI: https://doi.org/10.1056/NEJM199501053320101
8. Carmichael J, Bessell EM, Harris AL, et al. Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis. Br J Cancer. 1994;70:1161–4. doi: 10.1038/bjc.1994.465. DOI: https://doi.org/10.1038/bjc.1994.465
9. Ioannidis JP, Hesketh PJ, Lau J. Contribution of dexamethasone to control of chemotherapy-induced nausea and vomiting: a meta-analysis of randomized evidence. J Clin Oncol. 2000;18(19):3409–22. DOI: https://doi.org/10.1200/JCO.2000.18.19.3409
10. Geling O, Eichler HG. 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(6):1289–94. doi: 10.1200/jco.2005.04.022. DOI: https://doi.org/10.1200/JCO.2005.04.022
11. Italian Group for Antiemetic Research. Dexamethasone alone or in combination with ondansetron for the prevention of delayed nausea and vomiting induced by chemotherapy. N Engl J Med. 2000;342:1554–9. doi: 10.1056/nejm200005253422102. DOI: https://doi.org/10.1056/NEJM200005253422102
12. Jantunen IT, Kataja VV, Muhonen TT. An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. Eur J Cancer. 1997;33(1):66–74. doi: 10.1016/s0959-8049(96)00276-6. DOI: https://doi.org/10.1016/S0959-8049(96)00276-6
13. De Wit R, de Boer AC, van Linden GHM, et al. Effective cross-over to granisetron after failure to ondansetron, a randomized double-blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy. Br J Cancer. 2001;85:1099–101. DOI: https://doi.org/10.1054/bjoc.2001.2045
14. Passik SD, Loehrer PJ, Navari RJ, et al. A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients receiving chemotherapy: A Hoosier Oncology Group study. Proc ASCO. 2002;21:374. doi: 10.1081/cnv-200029066. DOI: https://doi.org/10.1081/CNV-200029066
15. Aapro MS, Thuerlimann B, Sessa C, et al. A randomized double-blind trial to compare the clinical efficacy of granisetron with metoclopramide, both combined with dexamethasone in the prophylaxis of chemotherapy-induced delayed emesis. Ann Oncol. 2003;14:291–7. doi: 10.1093/annonc/mdg075. DOI: https://doi.org/10.1093/annonc/mdg075
16. Roila F, Donati D, Tamberi S, Margutti G. Delayed emesis: incidence, pattern, prognostic factors and optimal treatment. Supp Care Cancer. 2002;10:88–95. doi: 10.1007/s005200100295. DOI: https://doi.org/10.1007/s005200100295
17. Grunberg SM, Osoba D, Hesketh PJ, et al. Evaluation of new antiemetic agents and definition of antineoplastic agent emetogenicity – an update. Supp Care Cancer. 2005;13:80–4. doi: 10.1007/s00520-004-0718-y. DOI: https://doi.org/10.1007/s00520-004-0718-y
18. Eisenberg P, MacKintosh FR, Ritch P, Cornett PA, Macciocchi A. Efficacy, safety and pharmacokinetics of palonosetron in patients receiving highly emetogeric, cisplatin-based chemotherapy: a dose-ranging, clinical study. Ann Oncol. 2004;15:330–7. doi: 10.1093/annonc/mdh047. DOI: https://doi.org/10.1093/annonc/mdh047
19. Rubenstein EB, Slusher BS, Rojas C, Navari RM. New approaches to chemotherapy-induced nausea and vomiting: from neuropharmacology to clinical investigations. Cancer J. 2006;12:341–7. doi: 10.1097/00130404-200609000-00003. DOI: https://doi.org/10.1097/00130404-200609000-00003
20. Saito M, Aogi K, Sekine I, et al. 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;10:115–24. doi: 10.1016/s1470-2045(08)70313-9. DOI: https://doi.org/10.1016/S1470-2045(08)70313-9
21. Likhun Z, Xiang J, Xin D, Tao ZL. A Systematic Review and Meta-Analysis of Intravenous Palonosetron in the Prevention of Chemotherapy-Induced Nausea and Vomiting in Adults. The Oncologist. 2011;16:207–16. doi: 10.1634/theoncologist.2010-0198. DOI: https://doi.org/10.1634/theoncologist.2010-0198
22. Navari RM, Nagy CK, Gray SE. The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy. Supp Care Cancer. 2013;21(6):1655–63. doi: 10.1007/s00520-012-1710-6. DOI: https://doi.org/10.1007/s00520-012-1710-6
23. Herrstedt J, Aapro MS, Smyth JF, Del Favero A. Corticosteroids, dopamine antagonists and other drugs. Supp Care Cancer. 1998;6:204–14. doi: 10.1007/s005200050155. DOI: https://doi.org/10.1007/s005200050155
24. Tremblay PB, Kaiser R, Sezer O, et al. Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients. J Clin Oncol. 2003;21(11):2147–55. doi: 10.1200/jco.2003.05.164. DOI: https://doi.org/10.1200/JCO.2003.05.164
25. Kaiser R, Tremblay PB, Sezer O, et al. Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists. Pharmacogenetics. 2004;14(5):271–8. doi: 10.1097/00008571-200405000-00001. DOI: https://doi.org/10.1097/00008571-200405000-00001
26. Emend: EPAR. Scientific Discussion. European Medicine Agency; 2004. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000527/WC500026534.pdf.
27. 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. doi: 10.1200/jco.2010.31.7859. DOI: https://doi.org/10.1200/JCO.2010.31.7859
28. Ando Y, Hayashi T, Ito K, et al. Comparison between 5-day aprepitant and single-dose fosaprepitant meglumine for preventing nausea and vomiting induced by cisplatin-based chemotherapy. Supp Care Cancer. 2016; 24(2): 871–8. doi: 10.1007/s00520-015-2856-9. DOI: https://doi.org/10.1007/s00520-015-2856-9
29. Hesketh P, Rossi G, Rizzi G, et al. 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. 2014;25:1340–6. doi: 10.1093/annonc/mdu110. DOI: https://doi.org/10.1093/annonc/mdu110
30. Gralla R, Bosnjak S, Hontsa A, et al. A phase 3 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. 2014;25(7):1333–9. doi: 10.1093/annonc/mdu096. DOI: https://doi.org/10.1093/annonc/mdu096
31. Снеговой А.В., Манзюк Л.В. Роль ганатона в антиэметической терапии: новые возможности. Фарматека. 2011;20:85–8.
32. [Snegovoi AV, Manzyuk LV. Role of ganaton in antiemetic therapy: new opportunities. Farmateka. 2011;20:85–8. (In Russ)]
33. Снеговой А.В., Абрамов М.Е., Булавина И.С. и др. Практические рекомендации по профилактике и лечению тошноты и рвоты у онкологических больных. Злокачественные опухоли. 2015;4(спецвыпуск):327–37. doi: 10.18027/2224-5057-2015-4s-327-337.
34. [Snegovoi AV, Abramov ME, Bulavina IS, et al. Clinical guidelines for preventing nausea and vomiting in oncological patients. Zlokachestvennie opuholi. 2015;4(special issue):327–37. doi: 10.18027/2224-5057-2015-4s-327-337. (in Russ)]