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

J Clin Oncol. 1994 Nov;12(11):2439-46. doi: 10.1200/JCO.1994.12.11.2439.

Abstract

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 [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.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • 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
  • Tropisetron
  • Vomiting / chemically induced
  • Vomiting / prevention & control*

Substances

  • Antiemetics
  • Indoles
  • Pyrrolidines
  • Tropisetron
  • Dexamethasone
  • alizapride