The addition of ondansetron to the combination of metoclopramide, dexamethasone, and lorazepam did not improve vomiting prevention in patients receiving high-dose cisplatin.
BACKGROUND: Serotonin has been shown to be an important mediator of chemotherapy-induced vomiting. Ondansetron is a potent and highly specific antagonist of the 5-HT3 serotonin receptor. The objective of the current trial was to determine if the addition of ondansetron to the combination of metoclopramide, dexamethasone, and lorazepam (MDL) could improve the control of vomiting in patients receiving high-dose cisplatin. The three-drug MDL antiemetic regimen has been shown to prevent vomiting in 67% of patients receiving high-dose cisplatin. METHODS: Thirty-two patients receiving initial cisplatin (greater than or equal to 100 mg/m2) were given intravenous lorazepam, 1.5 mg/m2 (maximum dose, 3 mg), one dose 45 minutes before cisplatin; metoclopramide, 3 mg/kg 40 minutes before and 90 minutes after cisplatin; ondansetron, 0.3 mg/kg 25 minutes before and 3.5 hours after cisplatin; and dexamethasone, 20 mg, one dose 10 minutes before cisplatin. Patients were followed for 24 hours after cisplatin administration. RESULTS: Vomiting was prevented in 67% of patients (95% confidence interval, 47-83%). Adverse effects were mild and transient and included sedation, headache, serum aspartate transaminase, and alanine transaminase elevations, akathisia, and hiccups. CONCLUSIONS: Vomiting was prevented in two thirds of patients treated with MDL plus ondansetron, a result similar to that observed in earlier trials of MDL alone. The lack of improvement in emetic control by the addition of ondansetron suggests that vomiting mediated through 5-HT3 receptors is already effectively blocked. Emesis that occurs despite pretreatment with MDL is likely mediated by other mechanisms.