OPTIMAL COMBINATION THERAPY WITH TROPISETRON IN 445 PATIENTS WITH INCOMPLETE CONTROL OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING

Purpose: This study evaluated tropisetron (Navoban; Sandoz-Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. Patients and Methods: One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [IV] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg IV; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg IV and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. Results: Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. Conclusion: The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.