Corticosteroids have not been approved by the FDA for use as antiemetic
agents. However, the efficacy of these agents (primarily dexamethasone)
when used as single agents for control of emesis has been extensively
documented. In addition, dexamethasone, when used in combination
regimens, has been shown to increase the efficacy of conventional
antiemetics, such as metoclopramide and, recently, the 5-hydroxytryptamine
(5-HT3)-receptor antagonists ondansetron (Zofran) and granisetron
(Kytril), in preventing chemotherapy-induced acute emesis.
The improved efficacy of ondansetron when administered in combination
with dexamethasone in patients receiving cisplatin (Platinol)
chemotherapy has been confirmed in several randomized, double-blind
studies. In studies with intravenous ondansetron, complete protection
from emesis was achieved in 58% to 91% of patients receiving combination
therapy, as compared with 30% to 64% of those receiving ondansetron
alone (P less than 0.05) [1-5]. Smith and colleagues 
evaluated the use of oral ondansetron with cisplatin chemotherapy
and reported a complete response rate of 44% with ondansetron
plus dexamethasone vs only 7% with ondansetron alone (P
less than 0.05).
Similar results demonstrating improved efficacy with dexamethasone
have been published in two randomized, double-blind studies utilizing
a combination of oral or intravenous granisetron plus dexamethasone
[7,8]. In these studies, complete response at 24 hours occurred
in 65% of patients who received combination therapy vs 39% to
56% of those who received granisetron alone.
Two published studies have evaluated the efficacy of 5-HT3 -receptor
antagonists alone or in combination with dexamethasone in patients
receiving moderately emetogenic chemotherapy [9,10]. The Italian
Group for Antiemetic Research  compared granisetron alone,
dexamethasone alone, and the combination of granisetron plus dexamethasone
in patients receiving moderately emetogenic chemotherapy. Superior
antiemetic control (complete protection from vomiting) was demonstrated
with combination therapy, as compared with granisetron alone or
dexamethasone alone (93%, 72%, 71%, respectively; P less
than 0.001 for all comparisons).
Similarly, in the other study, granisetron plus dexamethasone
provided complete protection in 85% of patients vs 76% of patients
treated with granisetron alone (P = 0.053) . No prospective,
randomized studies are available to compare the efficacy of ondansetron
alone or in combination with dexamethasone in patients treated
with moderately emetogenic chemotherapy.
The mechanisms by which dexamethasone inhibits cytotoxic-induced
emesis are not clearly understood, although several have been
proposed. These include reduction of prostanoid turnover by inhibition
of arachidonic acid release, modulation of substances derived
from arachidonic acid metabolism (eg, lipoxygenase products),
and reduction of the amount of available serotonin by activation
of tryptophan pyrrolase, thereby shunting metabolism away from
serotonergic synthetic pathways [11,12]. Further studies are warranted
to elucidate the mechanisms of emesis control of dexamethasone.
The optimal dose of dexamethasone has not been established, but
most studies to date have utilized 20 mg given intravenously prior
to chemotherapy on the day of chemotherapy. However, divided or
lower doses of dexamethasone (eg, 10 mg) have not been adequately
Short courses of dexamethasone generally cause no or minimal adverse
effects; mild insomnia and epigastric discomfort may occur. Patients
with diabetes mellitus should be monitored for blood glucose elevations
following dexamethasone therapy.
Based on the accumulated data, ondansetron or granisetron should
be administered in combination with dexa- methasone whenever either
drug is used for the prevention of nausea and vomiting, unless
medical contraindications exist.
1. Hesketh PJ, Harvey WH, Harker WG, et al: A randomized, double-blind
comparison of intravenous ondansetron alone and in combination
with intravenous dexamethasone in the prevention of high-dose
cisplatin-induced emesis. J Clin Oncol 12:596-600, 1994.
2. Joss RA, Bacchi M, Buser K, et al: Ondansetron plus dexamethasone
is superior to ondansetron alone in the prevention of emesis in
chemotherapy-naive and previously treated patients. Ann Oncol
3. Roila F, Tonato M, Cognetti F, et al: Prevention of cisplatin-induced
emesis: A double-blind multicenter randomized crossover study
comparing ondansetron and ondansetron plus dexamethasone. J Clin
Oncol 9:675-678, 1991.
4. Smyth JF, Coleman RE, Nicolson M, et al: Does dexamethasone
enhance control of acute cisplatin-induced emesis by ondansetron?
Br Med J 303:1423-1426, 1991.
5. Tonato M, on behalf of the Italian Oncology Group for Clinical
Research: Ondansetron plus dexamethasone. Eur J Cancer 27(suppl
6. Smith DB, Newlands ES, Rustin GJS, et al: Comparison of ondansetron
and ondansetron plus dexamethasone as antiemetic prophylaxis during
cisplatin-containing chemotherapy. Lancet 338:487-490, 1991.
7. Heron JF, Goedhals L, Jordaan JP, et al, on behalf of the Granisetron
Study Group: Oral granisetron alone and in combination with dexamethasone.
Ann Oncol 5:579-584, 1994.
8. Latreille J, Stewart D, Laberge F, et al: Dexamethasone (DEX)
improves the efficacy of granisetron (GRAN) in the first 24 hours
following high-dose cisplatin (HDCP) chemotherapy (abstract).
Proc Am Soc Clin Oncol 12:133, 1993.
9. 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 70:1161-1164, 1994.
10. 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 332:1-5, 1995.
11. Andrews PLR, Davis CJ: The mechanism of emesis induced by
anti-cancer therapies, in Andrews PLR, Sanger GJ (eds): Emesis
in Anti-Cancer Therapy: Mechanisms and Treatment, pp 113-161.
London, Chapman & Hall Medical, 1993.
12. Woods AJ, Andrews PLR: Cisplatin acutely reduces 5-hydroxytryptamine-induced
vagal depolarization in the rat: Protective action of dexamethasone.
Eur J Pharmacol 278:275-278, 1995.