Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting

• Published in: Journal of clinical oncology Vol. 12; no. 11; p. 2439
• Main Authors: Hulstaert, F, Van Belle, S, Bleiberg, H, Canon, J L, Dewitte, M, Buyse, M, De Keyser, P, Westelinck, K J
• Format: Journal Article
• Language: English
• Published: United States 01.11.1994
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics - administration & dosage; Antiemetics - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Dexamethasone - pharmacology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Interactions; Female; Humans; Indoles - administration & dosage; Indoles - therapeutic use; Injections, Intravenous; Male; Middle Aged; Nausea - chemically induced; Nausea - prevention & control; Prognosis; Prospective Studies; Pyrrolidines - administration & dosage; Pyrrolidines - therapeutic use; Vomiting - chemically induced; Vomiting - prevention & control
• ISSN: 0732-183X
• DOI: 10.1200/JCO.1994.12.11.2439

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. 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 [i.v.] 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 i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. 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. 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. 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.