PHASE-III DOUBLE-BLIND COMPARISON OF DOLASETRON MESYLATE AND ONDANSETRON AND AN EVALUATION OF THE ADDITIVE ROLE OF DEXAMETHASONE IN THE PREVENTION OF ACUTE AND DELAYED NAUSEA AND VOMITING DUE TO MODERATELY EMETOGENIC CHEMOTHERAPY

Purpose: To compare the efficacy of dolasetron and ondansetron in cont rolling nausea and vomiting in the first 24 hours; to evaluate the eff icacy when dexamethasone is added to either drug in the first 24 hours ; and to extend these comparisons over 7 days in patients receiving mo derately emetogenic chemotherapy. Patients and Methods: This was a mul ticenter, double-blind, randomized study with six parallel arms that u sed a 2 x 2 factorial design in chemotherapy-naive patients. In arm 1, dolasetron (2.4 mg/kg) was given intravenously (IV) prechemotherapy, followed 24 hours later by oral dolasetron (200 mg once daily) for 6 d ays. Arms 2 and 3 consisted of dolasetron and dexamethasone 8 mg IV, f ollowed 24 hours later by oral dexamethasone (8 mg once daily) in one arm, and oral dexamethasone and dolasetron in the other, also for 6 da ys. In arms 4, 5, and 6, ondansetron (32 mg IV or 8 mg orally twice da ily) was administered in a similar manner to arms 1, 2, and 3 before a nd 24 hours after chemotherapy. Mean nausea severity (MNS) was assesse d on a visual analog scale (VAS) in a daily diary. Results: Of 703 pat ients enrolled, 696 were eligible. There were 343 dolasetron- and 353 ondansetron-treated patients; 57% of dolasetron-treated patients had c omplete protection in the first 24 hours versus 67% of patients who re ceived ondansetron (P =.013). MNS was also more pronounced on the dola setron arm (P = .051). Sixty-seven percent of patients who received ad ded dexamethasone in the first 24 hours had complete protection, compa red with 55% without dexomethasone (P < .001). MNS was significantly r educed with the addition of dexamethasone (P < .001). At 7 days, dolas etron and ondansetron had equivalent complete protection rates (36% an d 39%, respectively). With the addition of dexamethasone, 48% of patie nts compared with 28% had complete protection (P < .001). MNS was sign ificantly improved with added dexamethasone (P < .001). Conclusion: At the doses used, dolasetron was significantly less effective than onda nsetron at controlling nausea and vomiting in the first 24 hours in pa tients receiving moderately emetogenic chemotherapy, but there wets no demonstrable difference between both drugs over 7 days. The addition of dexamethasone significantly improved the efficacy of both drugs in the first 24 hours and over 7 days. (C) 1997 by American Society of Cl inical Oncology.