Double-blind, dose-finding study of four intravenous doses of dexamethasone in the prevention of cisplatin-induced acute emesis. Italian Group for Antiemetic Research.

PURPOSE: A 5-hydroxytryptamine 3 (5-HT3) receptor antagonist plus dexamethasone is the most efficacious antiemetic prophylactic treatment for the prevention of cisplatin-induced acute emesis, but the optimal intravenous (i.v.) dose of dexamethasone is unknown. This prompted us to perform a multicenter, randomized, double-blind, dose-finding study that compared four different doses of dexamethasone. PATIENTS AND METHODS: Patients were randomized to receive dexamethasone, either 4, 8, 12, or 20 mg, administered by 15-minute i.v. infusion 45 minutes before cisplatin. Ondansetron 8 mg was added to dexamethasone and was administered i.v. 30 minutes before cisplatin. From March 1996 to July 1997, 531 patients were enrolled onto the study and 530 were assessable according to the intention-to-treat principle (133 patients received 4 mg; 136 patients, 8 mg; 130 patients, 12 mg; and 131 patients, 20 mg of dexamethasone). RESULTS: Complete protection from acute vomiting and nausea was achieved by 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 < .005) and was superior, but not significantly, compared with those who received 12 mg. Complete protection from nausea was superior, but not significantly, in patients who received 20 mg of dexamethasone. Multifactorial analysis confirmed these results. Antiemetic treatment was well tolerated, and no significant difference was found among the four groups in the incidence of adverse events. CONCLUSION: A 20-mg single i.v. dose of dexamethasone should be considered the most efficacious prophylactic dose for the prevention of cisplatin-induced acute emesis.