DOUBLE-BLIND, DOSE-FINDING STUDY OF 4 INTRAVENOUS DOSES OF DEXAMETHASONE IN THE PREVENTION OF CISPLATIN-INDUCED ACUTE EMESIS

Purpose: A 5-hydroxytryptamine 3 (5-HT3) receptor antagonist plus dexa methasone is the most efficacious antiemetic prophylactic treatment fo r the prevention of cisplatin-induced acute emesis, but the optimal in travenous (IV) dose of dexamethasone is unknown. This prompted us to p erform a multicenter, randomized, double-blind, dose-finding study tha t 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 IV infusion 45 minutes before cisp latin. Ondansetron 8 mg was added to dexamethasone and was administere d IV 30 minutes before cisplatin. From March 1996 to July 1997, 531 pa tients were enrolled onto the study and 530 were assessable according to the intention-to-treat principle (133 patients received 4 mg; 136 p atients, 8 mg; 130 patients, 12 mg; and 131 patients, 20 mg of dexamet hasone). Results: Complete protection from acute vomiting and nausea w as 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 fr om 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 rec eived 12 mg. Complete protection from nausea was superior, but not sig nificantly, in patients who received 20 mg of dexamethasone. Multifact orial analysis confirmed these results. Antiemetic treatment was well tolerated, and no significant difference was found among the four grou ps in the incidence of adverse events. Conclusion: A 20-mg single IV d ose of dexamethasone should be considered the most efficacious prophyl actic dose for the prevention of cisplatin-induced acute emesis. J Cli n Oncol 16:2937-2942. (C) 1998 by American Society of Clinical Oncolog y.