Dexamethasone for Nausea: Is There an Optimal Dose?
October 1, 1998
Dexamethasone for Nausea: Is There an Optimal Dose?
ABSTRACT & COMMENTARY
Synopsis: In this multicenter trial, dexamethasone was shown to have a dose-response effect in reducing nausea and vomiting in cancer patients receiving cisplatin. The highest tested dose (20 mg) administered in conjunction with ondansetron (8 mg) was most successful in reducing both nausea and vomiting. There were no significant acute adverse effects with dexamethasone, even at this higher dose. Thus, for patients receiving cisplatin alone or in combination with other drugs, the 20 mg dose of dexamethasone seems most appropriate.
Source: The Italian Group for Antiemetic Research. J Clin Oncol 1998;16:2937-2942.
Although there has been convincing clinical experience with dexamethasone as an anti-emetic agent, the optimal dose has not been clearly defined. This prompted an Italian group of investigators to perform a multicenter, randomized, double-blind, dose-finding study comparing four different doses of dexamethasone. Patients (n = 531) were randomized to receive either 4, 8, 12, or 20 mg of dexamethasone administered by 15-minute IV infusion 45 minutes before cisplatin. Ondansetron (8 mg) was given to all patients 30 minutes before cisplatin. Complete protection from nausea and vomiting was achieved in 69.2% and 60.9% of patients, respectively, who received 4 mg of dexamethasone, by 69.1% and 61.0% of those who received 8 mg, by 78.5% and 66.9% of those who received 12 mg, and by 83.2% and 71.0% of those who received 20 mg of dexamethasone. Complete protection from vomiting was significantly superior in patients who received 20 mg compared with those who received 4 and 8 mg of dexamethasone (P < 0.005) and was superior, but not significantly, to that seen in patients who received 12 mg. Antiemetic treatment was well-tolerated by the groups and there was no significant difference in the appearance of adverse reactions among the four groups. Thus, the group concludes that a 20 mg single IV dose of dexamethasone should be considered the most efficacious prophylactic dose for the prevention of cisplatin-induced acute emesis.
COMMENTARY
Occasionally, widespread clinical practice precedes careful investigation, and such has been the case with dexamethasone as an antiemetic. There have been only a few published reports on its efficacy.1,2 Nonetheless, clinicians have been quick to adopt dexamethasone treatment for this application because its benefits were readily apparent. However, there has been confusion about dose and schedule. This multicenter trial has answered some of the questions.
Although the study lacked a no treatment group, the efficacy of dexamethasone can be inferred from the apparent dose response curve. Furthermore, clinical experience with cisplatin alone or in combination with other agents would predict that ondansetron alone would not have been as effective as the results reported herein with the combination of ondansetron and dexamethasone. The highest dose selected (20 mg) was most effective. It remains to be seen if higher doses would lead to even better control.
Certainly, not all patients were protected by the combination. In fact, one curious observation was that the dose effect disappeared when examining patients who received high-dose cisplatin (e.g., doses > 90 mg/m2). For these patients, complete protection from vomiting was 68.5%, 66.7%, 75.5%, and 71.9% for the groups treated with 4, 8, 12, and 20 mg of dexamethasone, respectively. The reason for this is not clear. It is possible that higher doses of dexamethasone would be more effective, but this remains to be tested.
Another question that remains to be answered is the role of dexamethasone in drug regimens with less emetogenic potential. Although no short-term toxicity was apparent, there remains concern for those receiving weekly chemotherapy in whom repeated injection of a glucocorticoid, especially at higher doses, might have accumulated toxicity. In these patients, alternative pharmacological approaches would seem prudent.