ONDANSETRON PLUS DEXAMETHASONE IS SUPERIOR TO ONDANSETRON ALONE IN THE PREVENTION OF EMESIS IN CHEMOTHERAPY-NAIVE AND PREVIOUSLY TREATED PATIENTS

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 t heir first course of highly emetogenic chemotherapy and in chemotherap y-pretreated patients refractory to standard anti-emetics. Patients an d methods: Patients were randomized to receive either 20 mg dexamethas one as an intravenous infusion or placebo plus ondansetron 8 mg 15 min utes prior to and 4 and 8 hours after the administration of chemothera py. According to the randomisation code patients received from day 2 t o 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 dail y. Patients undergoing multiple-day treatment received intravenous stu dy 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 t he combination of ondansetron plus dexamethasone was significantly sup erior to ondansetron plus placebo in protecting the patients completel y from emesis (retching and vomiting) (81% versus 64%, p = 0.04). The mean number of vomiting episodes was significantly lower in the ondans etron-plus-dexamethasone-treated patients than in those receiving onda nsetron plus placebo (0.8 versus 2.1, p = 0.03). In this group of pati ents there was significantly superior protection from emesis on the se cond 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 v omiters the combination of ondansetron plus dexamethansone was superio r to ondansetron plus placebo in protecting the patients from acute em esis, with 70% versus 48% of the patients being completely protected ( p = 0.03). The mean number of vomiting episodes was significantly lowe r 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 p rotection from nausea, retching and vomiting compared to 35% in the on dansetron-plus-placebo-treated group (p = 0.05). Overall 22% of the pa tients (20% in the ondansetron-plus-placebo and 25% in the ondansetron -plus-dexamethasone arm) experienced at least one, usually mild, adver se event. More patients in the ondansetron-plus-dexamethasone arm comp lained of epigastric pain or burning (8/101 versus 4/112, p-value = 0. 16). The difference in patients reporting constipation (6/1 01 versus 0/112) was highly significant at a p-value of 0.008. Conclusions: The combination of dexamethasone plus ondansetron is more effective in pro tecting chemotherapy-naive patients undergoing their first course of h ighly emetogenic chemotherapy with cisplatin and chemotherapy-pretreat ed patients refractory to standard antiemetics from chemotherapy-induc ed nausea and vomiting compared to ondansetron plus placebo.