Chonnam Med J.  2010 Aug;46(2):88-93. 10.4068/cmj.2010.46.2.88.

Efficacy according to Dexamethasone Dose in Combination with Aprepitant and Granisetron during Cisplatin-based Chemotherapy

Affiliations
  • 1Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. ijchung@chonnam.ac.kr

Abstract

The purpose of this study was to evaluate the dosage of dexamethasone in combination with granisetron and aprepitant when used for the prevention of acute and delayed nausea and vomiting in patients receiving high-dose cisplatin chemotherapy. The study was retrospective. Ninety-two patients received cisplatin (> or =50 mg/m2) and either a high-dose (Group I, n=57) or low-dose (Group II, n=35) regimen of dexamethasone. The high-dose regimen consisted of intravenous administration of 20 mg on day 1 and 8 mg on days 2~4. The low-dose regimen consisted of intravenous administration of 10 mg before cisplatin and oral dexamethasone 4 mg on days 2~4. Both groups received granisetron and aprepitant. The primary endpoint was complete response over 5 days following cisplatin administration. In the acute phase, complete response occurred in 87.7% of Group I and 91.4% of Group II patients (p=0.58). In the delayed phase, the proportions of patients without emesis in Groups I and II were 84.2% and 65.7%, respectively (p=0.04). In the overall phase, the complete response rates in Groups I and II were 80.7% and 65.7%, respectively (p=0.11). The high-dose dexamethasone regimen is superior to the low-dose in preventing delayed chemotherapy-induced nausea and vomiting, with no significant differences evident in the acute and overall phases. The high-dose dexamethasone regimen should be considered as a standard antiemetic therapy for cisplatin-treated patients.

Keyword

Chemotherapy; Dexamethasone; Nausea; Vomiting

MeSH Terms

Administration, Intravenous
Cisplatin
Dexamethasone
Granisetron
Humans
Morpholines
Nausea
Retrospective Studies
Vomiting
Cisplatin
Dexamethasone
Granisetron
Morpholines

Reference

1. Morran C, Smith DC, Anderson DA, McArdle CS. Incidence of nausea and vomiting with cytotoxic chemotherapy: a prospective randomised trial of antiemetics. Br Med J. 1979. 1:1323–1324.
Article
2. Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997. 15:103–109.
Article
3. Leibundgut U, Lancranjan I. First results with ICS 205-930 (5-HT3 receptor antagonist) in prevention of chemotherapy-induced emesis. Lancet. 1987. 1:1198.
Article
4. Ballatori E, Roila F, De Angelis V, Ciccarese G, Palladino MA, Tonato M, et al. Clinical and methodological issues in antiemetic therapy: a worldwide survey of experts' opinions. Multinational association of supportive care in cancer. Support Care Cancer. 1997. 5:269–273.
Article
5. 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. American Society of Clinical Oncology. J Clin Oncol. 1999. 17:2971–2994.
6. 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. 21:4112–4119.
Article
7. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, Julie Ma G, Eldridge K, Hipple A, et al. 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. 97:3090–3098.
Article
8. Jordan K, Kasper C, Schmoll HJ. Chemotherapy-induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment. Eur J Cancer. 2005. 41:199–205.
Article
9. Grunberg SM. Antiemetic activity of corticosteroids in patients receiving cancer chemotherapy: dosing, efficacy, and tolerability analysis. Ann Oncol. 2007. 18:233–240.
Article
10. Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, et al. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol. 2006. 24:2932–2947.
Article
11. Italian Group For Antiemetic Research. Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide. J Clin Oncol. 2004. 22:725–729.
12. Italian Group for Antiemetic Research. Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. J Clin Oncol. 1998. 16:2937–2942.
13. McCrea JB, Majumdar AK, Goldberg MR, Iwamoto M, Gargano C, Panebianco DL, et al. Effects of the neurokinin1 receptor antagonist aprepitant on the pharmacokinetics of dexamethasone and methylprednisolone. Clin Pharmacol Ther. 2003. 74:17–24.
Article
14. Blum RA, Majumdar A, McCrea J, Busillo J, Orlowski LH, Panebianco D, et al. Effects of aprepitant on the pharmacokinetics of ondansetron and granisetron in healthy subjects. Clin Ther. 2003. 25:1407–1419.
Article
15. Williams SD, Birch R, Einhorn LH, Irwin L, Greco FA, Loehrer PJ. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med. 1987. 316:1435–1440.
Article
16. Roila F, Tonato M, Cognetti F, Cortesi E, Favalli G, Marangolo M, et al. Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. J Clin Oncol. 1991. 9:675–678.
Article
17. Cunningham D, Hawthorn J, Pople A, Gazet JC, Ford HT, Challoner T, et al. Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet. 1987. 1:1461–1463.
Article
18. Kris MG, Gralla RJ, Clark RA, Tyson LB. Dose-ranging evaluation of the serotonin antagonist GR-C507/75 (GR38032F) when used as an antiemetic in patients receiving anticancer chemotherapy. J Clin Oncol. 1988. 6:659–662.
Article
19. Olver I, Paska W, Depierre A, Seitz JF, Stewart DJ, Goedhals L, et al. A multicentre, double-blind study comparing placebo, ondansetron and ondansetron plus dexamethasone for the control of cisplatin-induced delayed emesis. Ondansetron delayed emesis study group. Ann Oncol. 1996. 7:945–952.
Article
20. Kris MG, Gralla RJ, Clark RA, Tyson LB, O'Connell JP, Wertheim MS, et al. Incidence, course, and severity of delayed nausea and vomiting following the administration of high-dose cisplatin. J Clin Oncol. 1985. 3:1379–1384.
Article
21. Hesketh PJ. Potential role of the NK1 receptor antagonists in chemotherapy-induced nausea and vomiting. Support Care Cancer. 2001. 9:350–354.
Article
22. Saito R, Takano Y, Kamiya HO. Roles of substance P and NK(1) receptor in the brainstem in the development of emesis. J Pharmacol Sci. 2003. 91:87–94.
Article
23. Hargreaves R. Imaging substance P receptors (NK1) in the living human brain using positron emission tomography. J Clin Psychiatry. 2002. 63:Suppl 11. 18–24.
24. Grunberg SM, Hesketh PJ. Control of chemotherapy-induced emesis. N Engl J Med. 1993. 329:1790–1796.
Article
25. Kris MG, Radford JE, Pizzo BA, Inabinet R, Hesketh A, Hesketh PJ. Use of an NK1 receptor antagonist to prevent delayed emesis after cisplatin. J Natl Cancer Inst. 1997. 89:817–818.
Article
26. Grélot L, Dapzol J, Estéve E, Frugiére A, Bianchi AL, Sheldrick RL, et al. Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist. Br J Pharmacol. 1998. 124:1643–1650.
Article
27. Warr DG, Grunberg SM, Gralla RJ, Hesketh PJ, Roila F, Wit R, et al. 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. 2005. 41:1278–1285.
Article
Full Text Links
  • CMJ
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr