Skip to main content

Advertisement

SpringerLink
Log in

Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin

  • Original Article—Alimentary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1.

Methods

Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m2) and S-1 (80 mg/m2) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0–120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0–24 h), and delayed (24–120 h) phases.

Results

Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7 % of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9 %. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5 % of patients reported “minimal or no impact of CINV on daily life”.

Conclusions

Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Bender CM, McDaniel RW, Murphy-Ende K, Pickett M, Rittenberg CN, Rogers MP, et al. Chemotherapy-induced nausea and vomiting. Clin J Oncol Nurs. 2002;6:94–102.

    Article  PubMed  Google Scholar 

  2. de Boer-Dennert M, de Wit R, Schmitz PI, Djontono J, v Beurden V, Stoter G, et al. Patient perceptions of the side effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer. 1997;76:1055–61.

    Google Scholar 

  3. Hickok JT, Roscoe JA, Morrow GR, King DK, Atkins JN, Fitch TR. Nausea and emesis remain significant problems of chemotherapy despite prophylaxis with 5-hydroxytryptamine-3 antiemetics: a University of Rochester James P. Wilmot Cancer Center Community Clinical Oncology Program Study of 360 cancer patients treated in the community. Cancer. 2003;97:2880–6.

    Article  CAS  PubMed  Google Scholar 

  4. Lindley CM, Hirsch JD, O’Neill CV, Transau MC, Gilbert CS, Osterhaus JT. Quality of life consequences of chemotherapy-induced emesis. Qual Life Res. 1992;1:331–40.

    Article  CAS  PubMed  Google Scholar 

  5. Bloechl-Daum B, Deuson RR, Mavros P, Hansen M, Herrstedt J. 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.

    Article  CAS  PubMed  Google Scholar 

  6. Ihbe-Heffinger A, Ehlken B, Bernard R, Berger K, Peschel C, Eichler HG, et al. The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Ann Oncol. 2004;15:526–36.

    Article  CAS  PubMed  Google Scholar 

  7. Tavorath R, Hesketh PJ. Drug treatment of chemotherapy-induced delayed emesis. Drugs. 1996;52:639–48.

    Article  CAS  PubMed  Google Scholar 

  8. Ettinger DS, Bierman PJ, Bradbury B, Comish CC, Ellis G, Ignoffo RJ, et al. Antiemesis. J Natl Compr Canc Netw. 2007;5:12–33.

    CAS  PubMed  Google Scholar 

  9. du Bois A, Meerpohl HG, Vach W, Kommoss FG, Fenzl E, Pfleiderer A. Course, patterns, and risk-factors for chemotherapy-induced emesis in cisplatin-pretreated patients: a study with ondansetron. Eur J Cancer. 1992;28:450–7.

    Article  PubMed  Google Scholar 

  10. Hesketh PJ. Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. Oncologist. 1999;4:191–6.

    CAS  PubMed  Google Scholar 

  11. Kris MG, Cubeddu LX, Gralla RJ, Cupissol D, Tyson LB, Venkatraman E, et al. Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin. Cancer. 1996;78:2193–8.

    Article  CAS  PubMed  Google Scholar 

  12. Aapro MS, Alberts DS. High-dose dexamethasone for prevention of cisplatin-induced vomiting. Cancer Chemother Pharmacol. 1981;7:11–4.

    Article  CAS  PubMed  Google Scholar 

  13. Gralla RJ, Osoba D, Kris MG, Kirkbride P, Hesketh PJ, Chinnery LW, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. J Clin Oncol. 1999;17:2971–94.

    CAS  PubMed  Google Scholar 

  14. 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;33:66–74.

    Article  CAS  PubMed  Google Scholar 

  15. Latreille J, Pater J, Johnston D, Laberge F, Stewart D, Rusthoven J, et al. Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 1998;16:1174–8.

    CAS  PubMed  Google Scholar 

  16. Tsukada H, Hirose T, Yokoyama A, Kurita Y. Randomised comparison of ondansetron plus dexamethasone with dexamethasone alone for the control of delayed cisplatin-induced emesis. Eur J Cancer. 2001;37:2398–404.

    Article  CAS  PubMed  Google Scholar 

  17. Hesketh PJ, Van Belle S, Aapro M, Tattersall FD, Naylor RJ, Hargreaves R, et al. Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists. Eur J Cancer. 2003;39:1074–80.

    Article  CAS  PubMed  Google Scholar 

  18. Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R, et al. 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. 2003;21:4112–9.

    Article  CAS  PubMed  Google Scholar 

  19. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, et al. Aprepitant Protocol 054 Study Group. 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. 2003;97:3090–8.

    Google Scholar 

  20. Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K, et al. Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol. 2006;17:1000–6.

    Article  CAS  PubMed  Google Scholar 

  21. Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, 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(Supplement 5):v232–43.

    Article  PubMed  Google Scholar 

  22. Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29: 4189–98.

    Google Scholar 

  23. JSCO Guidelines for Antiemetics in Oncology 2010. 1st ed. Tokyo: Kanehara shuppan; 2010.

  24. Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008;9:215–21.

    Article  CAS  PubMed  Google Scholar 

  25. Martin AR, Pearson JD, Cai B, Elmer M, Horgan K, Lindley C. Assessing the impact of chemotherapy-induced nausea and vomiting on patients’ daily lives: a modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall. Support Care Cancer. 2003;11:522–7.

    Article  CAS  PubMed  Google Scholar 

  26. Satou A, Yamazaki T, Nukariya N, Nakamachi M, Shimada K, Matsukawa M, et al. Development of a Japanese version of the FLIE. Gan To Kagaku Ryoho. 2002;29:281–91.

    PubMed  Google Scholar 

  27. Stephenson J, Davies A. An assessment of aetiology-based guidelines for the management of nausea and vomiting in patients with advanced cancer. Support Care Cancer. 2006;14:348–53.

    Article  PubMed  Google Scholar 

  28. Tonini G, Vincenzi B, Santini D. New drugs for chemotherapy-induced nausea and vomiting: focus on palonosetron. Expert Opin Drug Metab Toxicol. 2005;1:143–9.

    Article  CAS  PubMed  Google Scholar 

  29. Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C, et al. 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;14:1570–7.

    Article  CAS  PubMed  Google Scholar 

  30. Grote T, Hajdenberg J, Cartmell A, Ferguson S, Ginkel A, Charu V. Combination therapy for chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: palonosetron, dexamethasone and aprepitant. J Support Oncol. 2006;4:403–8.

    CAS  PubMed  Google Scholar 

  31. Herrington JD, Jaskiewicz AD, Song J. 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. 2008;112:2080–7.

    Article  CAS  PubMed  Google Scholar 

  32. Grunberg SM, Dugan M, Muss H, Wood M, Burdette-Radoux S, Weisberg T, Siebel M, et al. 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. 2009;17:589–94.

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Gastroenterological Surgery, Kanazawa University, 13-1, Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Katsunobu Oyama, Sachio Fushida, Tomoya Tsukada, Jun Kinoshita, Takashi Fujimura & Tetsuo Ohta

  2. Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan

    Masahide Kaji

  3. Department of Surgery, Public Central Hospital of Matto Ishikawa, Hakusan, Japan

    Toshiya Takeda

  4. Department of General and Digestive Surgery, Kanazawa Medical University, Kahoku, Japan

    Shinichi Kinami

  5. First Department of Surgery, University of Fukui, Fukui, Japan

    Yasuo Hirono

  6. Department of Surgery, Toyama Rosai Hospital, Uozu, Japan

    Katsuhiro Yoshimoto

  7. Department of Surgery, Takaoka City Hospital, Takaoka, Japan

    Kazuhisa Yabushita

  8. Department of Surgery, Toyama City Hospital, Toyama, Japan

    Hisashi Hirosawa

  9. Department of Gastroenterology, Keiju Medical Center, Nanao, Japan

    Yuki Takai

  10. Department of Surgery, Asanogawa General Hospital, Kanazawa, Japan

    Tatsuo Nakano

  11. Department of Surgery, NTT West Kanazawa Hospital, Kanazawa, Japan

    Hironobu Kimura

  12. Department of Surgery, Kanazawa Social Insurance Hospital, Kanazawa, Japan

    Toshiaki Yasui

  13. Department of Surgery, Kurobe City Hospital, Kurobe, Japan

    Atsushi Tsuneda

Authors
  1. Katsunobu Oyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sachio Fushida
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahide Kaji
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshiya Takeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shinichi Kinami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasuo Hirono
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Katsuhiro Yoshimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kazuhisa Yabushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hisashi Hirosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yuki Takai
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tatsuo Nakano
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hironobu Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Toshiaki Yasui
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Atsushi Tsuneda
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Tomoya Tsukada
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Jun Kinoshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Takashi Fujimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Tetsuo Ohta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katsunobu Oyama.

Additional information

For the Digestive Disease Support Organization (DDSO).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oyama, K., Fushida, S., Kaji, M. et al. Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin. J Gastroenterol 48, 1234–1241 (2013). https://doi.org/10.1007/s00535-012-0746-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00535-012-0746-1

Keywords

Search

Navigation