Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naive and previously treated patients. Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: This prospective, randomized, double-blind study assessed whether the addition of dexamethasone to ondansetron leads to improved control of chemotherapy--induced emesis, both in patients undergoing their first course of highly emetogenic chemotherapy and in chemotherapy-pretreated patients refractory to standard anti-emetics. PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasone as an intravenous infusion or placebo plus ondansetron 8 mg 15 minutes prior to and 4 and 8 hours after the administration of chemotherapy. According to the randomisation code patients received from day 2 to day 5 either ondansetron 8 mg p.o. + placebo p.o., three times daily, or ondansetron 8 mg p.o. + dexamethasone 4 mg p.o., three times daily. Patients undergoing multiple-day treatment received intravenous study treatment on the days of chemotherapy and thereafter oral treatment as outlined above. RESULTS: A total of 215 patients were entered into the study. Of these, 207 were evaluable (111 previously-untreated and 96 previously-treated patients). In the chemotherapy-naive patients the combination of ondansetron plus dexamethasone was significantly superior to ondansetron plus placebo in protecting the patients completely from emesis (retching and vomiting) (81% versus 64%, p = 0.04). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated patients than in those receiving ondansetron plus placebo (0.8 versus 2.1, p = 0.03). In this group of patients there was significantly superior protection from emesis on the second day (p-value = 0.04), and a trend towards a better protection on the third and fourth days. On each day the active combination offered better protection from nausea with an approximately 20% difference in favor of ondansetron plus dexamethasone. In the group of established vomiters the combination of ondansetron plus dexamethansone was superior to ondansetron plus placebo in protecting the patients from acute emesis, with 70% versus 48% of the patients being completely protected (p = 0.03). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated-patients than in those receiving ondansetron plus placebo (0.9 versus 2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55% of the patients had complete protection from nausea, retching and vomiting compared to 35% in the ondansetron-plus-placebo-treated group (p = 0.05). Overall 22% of the patients (20% in the ondansetron-plus-placebo and 25% in the ondansetron-plus-dexamethasone arm) experienced at least one, usually mild, adverse event. More patients in the ondansetron-plus-dexamethasone arm complained of epigastric pain or burning (8/101 versus 4/112, p-value = 0.16). The difference in patients reporting constipation (6/101 versus 0/112) was highly significant at a p-value of 0.008. CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effective in protecting chemotherapy-naive patients undergoing their first course of highly emetogenic chemotherapy with cisplatin and chemotherapy-pretreated patients refractory to standard antiemetics from chemotherapy-induced nausea and vomiting compared to ondansetron plus placebo.