OPTIMUM ANTIEMETIC THERAPY FOR CISPLATIN-INDUCED EMESIS OVER REPEAT COURSES - ONDANSETRON PLUS DEXAMETHASONE COMPARED WITH METOCLOPRAMIDE, DEXAMETHASONE PLUS LORAZEPAM

Background: This study was undertaken to compare the efficacy and tole rability of ondansetron plus dexamethasone (O+D) with metoclopramide p lus dexamethasone plus lorazepam (M+D+L) over three consecutive course s of cisplatin chemotherapy. Patients and methods: This was an interna tional, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenousl y (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m (2)) chemotherapy. On the following 4 days they were treated with onda nsetron 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/m(2) i.v. (max 3 mg) prior to cisplat in chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. appr oximately 2 hours following the first dose of metoclopramide. Treatmen t for the following 4 days was metoclopramide 40 mg tds and dexamethas one 4 mg bd orally. Two hundred and thirty-seven patients were recruit ed into the study (117 patients received O+D and 120 received M+D+L). Results: On the first course of chemotherapy, O+D was significantly su perior 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 bet ter in the O+D group (48%) than in the M+D+L (26%, P = 0.003). The mos t commonly occurring adverse events in the O+D group were constipation (25%) and headache (19%). In the M+D+L group drowsiness (38% of patie nts), 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 re ported 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 Despite the inclusion of lorazepam, 14% of patients in the M+D+L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the inv estigators, were probably or almost certainly related to study medicat ion. Conclusion: This study shows that O+D is significantly more effec tive and better tolerated than M+D+L for the control of emesis and nau sea over a series of three courses of cisplatin chemotherapy.