Advertisement

Supportive Care in Cancer

, Volume 20, Issue 4, pp 849–855 | Cite as

Randomized, double-blinded, placebo-controlled trial of ondansetron plus dexamethasone with or without metoclopramide as antiemetic prophylaxis in patients receiving high-dose cisplatin in medical practice

  • Suthinee Ithimakin
  • Kanakorn Runglodvatana
  • Akarin Nimmannit
  • Charuwan Akewanlop
  • Vichien Srimuninnimit
  • Narong Keerativitayanan
  • Nopadol Soparattanapaisarn
  • Apirom Laocharoenkeat
Original Article

Abstract

Purposes

Ondansetron plus dexamethasone are standard antiemetic agents for highly emetogenic chemotherapy. Metoclopramide is a dopamine antagonist, which may enhance efficacy of ondansetron and dexamethasone. The objective of this study was to assess the efficacy and tolerability of metoclopramide added to standard antiemetic regimen for prophylaxis of cisplatin-induced emesis.

Methods

Patients who received ≥50 mg/m2 of cisplatin for the first time were given intravenous ondansetron and dexamethasone on day 1 and were randomized to receive either standard antiemetics (ondansetron 8 mg orally bid on days 2–5 and dexamethasone 8 mg orally bid on days 2–4) plus metoclopramide 20 mg orally qid on days 2–5 or a placebo. The primary endpoint was a complete response (CR) rate defined as no emesis and no rescue treatment over a 120-h period. Secondary endpoints included severity of nausea and vomiting, time to first emesis, quality of life, and adverse effects.

Results

Among 162 patients, 50 patients (60%) in the metoclopramide group and 42 patients (53%) in the control group achieved CR (p = 0.36). The mean times to first emesis in the metoclopramide and control groups were 88 and 75 h, respectively (p = 0.18). The degrees of nausea and vomiting in both groups were similar. Eleven patients (13%) in the metoclopramide group and 20 (25%) in the control group required rescue treatment (p = 0.05). Quality of life and adverse effects were not different between the two groups.

Conclusion

The addition of metoclopramide to ondansetron plus dexamethasone reduced the use of rescue medication, but did not affect complete response rate, quality of life or adverse effects.

Keywords

Emetogenic chemotherapy Anti-emetic Metoclopramide 

Notes

Acknowledgments

The study protocol was granted by the Siriraj Research Development Fund (managed by Routine to Research, R2R).

Conflicts of interest

The authors indicated no conflict of interest.

References

  1. 1.
    Cohen L, de Moor CA, Eisenberg P, Ming EE, Hu H (2007) Chemotherapy-induced nausea and vomiting: incidence and impact on patient quality of life at community oncology settings. Support Care Cancer 15:497–503PubMedCrossRefGoogle Scholar
  2. 2.
    Blanchard EM, Hesketh PJ (2008) Nausea and vomiting. In: Devita VT, Lawrence TS, Rosenberg SA (eds) Cancer principles & practice of oncology, 8th edn. Lippincott Williams & Wilkins, Philadelphia, pp 2639–2646Google Scholar
  3. 3.
    Chitapanarux I, Lorvidhaya V, Kamnerdsupaphon P, Sumitsawan Y, Tharavichitkul E, Sukthomya V et al (2007) Chemoradiation comparing cisplatin versus carboplatin in locally advanced nasopharyngeal cancer: randomized, non-inferiority, open trial. Eur J Cancer 43:1399–1406PubMedCrossRefGoogle Scholar
  4. 4.
    National Comprehensive Cancer Network (2009) Antiemesis. National Comprehensive Cancer Network Guideline Version 4.2009Google Scholar
  5. 5.
    Hesketh PJ, Gandara DR (1991) Serotonin antagonists: a new class of antiemetic agents. J Natl Cancer Inst 83:613–620PubMedCrossRefGoogle Scholar
  6. 6.
    Roila F, Warr D, Clarck-Snow RA, Tonato M, Gralla RJ, Einhorn LH et al (2005) Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer 13:104–108PubMedCrossRefGoogle Scholar
  7. 7.
    Herrstedt J (2008) Antiemetics: an update and the MASCC guidelines applied in clinical practice. Nat Clin Pract Oncol 5:32–43PubMedCrossRefGoogle Scholar
  8. 8.
    Kris MG, Hesketh PJ, Herrstedt J, Rittenberg C, Einhorn LH, Grunberg S et al (2005) Consensus proposals for the prevention of acute and delayed vomiting and nausea following high-emetic risk chemotherapy. Support Care Cancer 13:85–96PubMedCrossRefGoogle Scholar
  9. 9.
    Hesketh PJ, Harvey WH, Harker WG, Beck TM, Ryan T, Bricker LJ et al (1994) A randomized, double-blinded comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin induced emesis. J Clin Oncol 12:596–600PubMedGoogle Scholar
  10. 10.
    Hesketh PJ, Grunberg SM, Gralla RJ, Warr DG, Roila F, de Wit R 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 21:4112–4119PubMedCrossRefGoogle Scholar
  11. 11.
    Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie MG, Eldridge K, Hipple A 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 97:3090–3098PubMedCrossRefGoogle Scholar
  12. 12.
    Schmoll HJ, Aapro MS, Poli-Bigelli S, Kim HK, Park K, Jordan K 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 17:1000–1006PubMedCrossRefGoogle Scholar
  13. 13.
    Herrstedt J, Sigsgaard T, Boesgaard M, Jensen TP, Dombernowsky P (1993) Ondansetron plus metopimazine compared with ondansetron alone in patients receiving moderately emetogenic chemotherapy. N Engl J Med 328:1076–1080PubMedCrossRefGoogle Scholar
  14. 14.
    Pearson JD, Cai B, Elmer W, Horgan K, Lindley C (2003) 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 11:522–527PubMedCrossRefGoogle Scholar
  15. 15.
    Picus J, Martin MG (2008) Gastrointestinal complications of chemotherapy. In: Perry MC (ed) The chemotherapy source book, 14th edn. Lippincott Williams & Wilkins, Philadelphia, pp 197–208Google Scholar
  16. 16.
    Roila F, Ballatori E, Angelis VD, Tonato M, Favero AD (1997) Ondansetron versus metoclopramide, both combined with dexamethasone, in prevention of cisplatin-induced delayed emesis. J Clin Oncol 15:124–130Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Suthinee Ithimakin
    • 1
  • Kanakorn Runglodvatana
    • 1
  • Akarin Nimmannit
    • 2
  • Charuwan Akewanlop
    • 1
  • Vichien Srimuninnimit
    • 1
  • Narong Keerativitayanan
    • 1
  • Nopadol Soparattanapaisarn
    • 1
  • Apirom Laocharoenkeat
    • 3
  1. 1.Division of Medical Oncology, Department of Medicine, Faculty of MedicineSiriraj HospitalBangkokThailand
  2. 2.Office for Research and Development, Faculty of MedicineSiriraj HospitalBangkokThailand
  3. 3.Pharmacy DepartmentSiriraj HospitalBangkokThailand

Personalised recommendations