Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: Ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam

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Abstract
This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O+D) with metoclopramide plus dexamethasone plus lorazepam (M+D+L) over three consecutive courses of cisplatin chemotherapy. This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50–100 mg/m) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4mg bd orally. M+D+L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O+D and 120 received M+D+L). On the first course of chemotherapy, O+D was significantly superior to the M+D+L regimen for complete control of emesis (days 1–5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O+D and 20% of M+D+L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1–5 over the three courses was significantly better in the O+D group (48%) than in the M+D+L (26%, P = 0.003). The most commonly occurring adverse events in the O+D group were constipation (25%) and headache (19%). In the M+D+L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M+D+L group. Despite the inclusion of lorazepam, 14% of patients in the M+D+L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. This study shows that O+D is significantly more effective and better tolerated than M+D+L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

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