Oral ondansetron for the control of delayed emesis after cisplatin. Report of a phase II study and a review of completed trials to manage delayed emesis.
BACKGROUND: Despite excellent control of vomiting during the initial 24 hours after chemotherapy with combination antiemetics, most patients who receive cisplatin at doses of 120 mg/m2 experience delayed emesis 24-120 hours after chemotherapy. METHODS: Twenty patients receiving cisplatin (greater than or equal to 100 mg/m2) as initial chemotherapy were entered into this Phase II trial to test the effectiveness of oral ondansetron, a specific serotonin receptor (5-HT3) antagonist, in controlling delayed emesis. All patients received intravenous metoclopramide, dexamethasone, and lorazepam for the control of acute emesis 0-24 hours after receiving cisplatin. They then received ondansetron 16 mg orally three times a day for 4 days. RESULTS: Fifteen percent of those who were treated with oral ondansetron had complete control of delayed emesis during the entire 4-day period (95% confidence interval, 3-38%). No serious adverse events occurred. CONCLUSIONS: At the dose and schedule tested, oral ondansetron did not appear to control delayed emesis. Previous trials of programs to lessen this complication suggest that both metoclopramide and dexamethasone are effective in lessening delayed vomiting and that the combination of these drugs is more effective than placebo. Although in one trial ondansetron appeared to control delayed emesis in patients who received cisplatin at doses of 50-120 mg/m2, it was not superior to either placebo or metoclopramide in two randomized studies. Additional testing of the 5-HT3 antagonists, both alone and in combination, will be needed to establish their role in the management of this condition.