A randomized double-blind trial of ondansetron alone versus in combination with dexamethasone versus in combination with dexamethasone and lorazepam in the prevention of emesis due to cisplatin-based chemotherapy.

OBJECTIVE: To compare the effectiveness and side effects of antiemetic regimens using ondansetron alone (O) versus ondansetron plus dexamethasone (OD) versus ondansetron plus dexamethasone plus lorazepam (ODA) in the prevention of emesis induced by cisplatin-based chemotherapy.

DESIGN: Randomized, double-blind trial.

PATIENTS AND METHODS: In this study, 75 patients who were receiving cisplatin (60 mg/m2) on day 1 and 5-fluorouracil (1,000 mg/m2) on day 2 to day 6 were enrolled. Patients were randomized to one of three treatment regimens: O, OD, or ODA. The patients assigned to O regimen received ondansetron 8 mg intravenously as a loading dose 15 minutes prior to cisplatin, then 1 mg/h continuous i.v. infusion (24 mg/day) for 48 hours. OD regimen consisted of ondansetron given as above plus dexamethasone administered at a dose of 10 mg i.v. injection every 12 hours for 3 days. ODA regimen was OD regimen plus lorazepam administered at a dose of 0.5 mg orally every 6 hours for 3 days. To ensure blinding, O group patients received 10 ml placebo-saline i.v. injection every 12 hours for 3 days, and O and OD group patients received placebo tablets orally every 6 hours for 3 days.

RESULTS: One patient did not receive assigned antiemetic regimen and was excluded from the analysis. In the acute phase, complete control of emesis was seen in 85% of all patients, and there was no significant difference among the three groups (p = .442). Complete control of nausea during the acute phase was achieved in 10 patients (41.2%) treated with O regimen alone, in 23 patients (92.0%) treated with OD regimen, and in 16 patients (64.0%) treated with ODA regimen (p < .001). In the delayed phase, 68% of patients who received the three-drug combination (ODA) and 56% of patients who received the two-drug combination (OD) obtained complete control of emesis, as opposed to 29% who were given ondansetron alone (p < .021). The incidences of headache, flushing, dry mouth, hiccups, and constipation were mild and tolerable and did not differ among the three groups.

DISCUSSION: Ondansetron was very effective in the prevention of nausea and vomiting during the acute phase after cisplatin administration. In treating delayed nausea and vomiting, although the results of three regimens were still disappointing, the combination of ondansetron plus dexamethasone or plus lorazepam provided superior results. Patients who received the lorazepam-containing regimen appeared more comfortable and less restless than those who were given other regimens.