Randomized, double-blind, dose-finding study of dexamethasone in preventing acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide:

Abstract

Purpose: Different doses and schedules of dexamethasone, combined with a 5-HT3 antagonist, are used to prevent acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide. Therefore, we planned a randomized, double-blind, dose finding study aimed to identify the preferred dose and schedule of dexamethasone.

Patients and methods: All consecutive chemotherapy-naive patients enrolled onto study were randomly assigned to receive for the prevention of acute emesis, during the first 24 hours, one of the following dexamethasone regimens, in combination with ondansetron 8 mg intravenously (i.v. ): for arm A, 8 mg i.v. before chemotherapy plus 4 mg orally every 6 hours for four doses, starting at the same time of the chemotherapy; for arm B, 24 mg i.v. single dose before chemotherapy; and for arm C, 8 mg i.v. single dose before chemotherapy. All patients received from day 2 to 5 oral dexamethasone 4 mg b.i.d.

Results: A total of 587 patients were enrolled, and 585 were assessed according to the intention-to-treat principle (195 patients in each arm). The rate of complete protection from acute vomiting and nausea, respectively, was not significantly different among the three groups (arm A, 84.6% and 66.7%; arm B, 83.6% and 56.9%; arm C, 89.2% and 61.0%), nor was the rate of complete protection from delayed vomiting and nausea, respectively (arm A, 81.0% and 46.7%; arm B, 81.3% and 45.1%; arm C, 79.8% and 46.1%). The incidence of delayed vomiting and nausea was strictly dependent on the presence of acute vomiting and nausea. Adverse events were mild and not significantly different among the three groups.

Conclusion: Dexamethasone 8 mg single dose i.v. before chemotherapy, in combination with a 5-HT3 antagonist, should be considered the preferred dose to prevent acute emesis induced by anthracyclines, carboplatin, or cyclophosphamide.