Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting

• Published in: Annals of oncology Vol. 5; no. 9; pp. 821 - 825
• Main Authors: Van Belle, S. J.-P., Stamatakis, L., Bleiberg, H., Cocquyt, V. F. J., Michel, J., de Bruijn, K. M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.1994
• Subjects: Adult; Aged; Aged, 80 and over; antiemetics; Antiemetics - administration & dosage; Antiemetics - adverse effects; Biological and medical sciences; chemically induced; Cisplatin - adverse effects; Drug Administration Schedule; drug therapy; Drug toxicity and drugs side effects treatment; Female; Humans; Indoles - administration & dosage; Indoles - adverse effects; Male; Medical sciences; Middle Aged; nausea; Nausea - chemically induced; Nausea - drug therapy; Neoplasms - drug therapy; Pharmacology. Drug treatments; therapeutic use; Toxicity: digestive system; Tropisetron; vomiting; Vomiting - chemically induced; Vomiting - prevention & control; Antineoplastic agent; Human; Intravenous administration; Toxicity; Multicenter study; Single dose; Posology; Dose activity relation; Prevention; Randomization; Vomiting; Digestive diseases; Antagonist; Antiemetic; Platinum II Complexes; 5-HT3 receptor
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/oxfordjournals.annonc.a059011

Background The purpose of these two studies was to define the optimal therapeutic dose of the 5-HT3 receptor antagonist tropisetron (Navoban®, ICS 205–930) in cisplatin-induced nausea and vomiting. Patients and methods In two multicentre, dose-finding studies of tropisetron in the prevention of cisplatin-induced emesis, cancer patients naïve to chemotherapy or who had not vomited previously were randomly assigned to tropisetron 5, 10, 20 or 40 mg (study I, 143 patients) or 2 or 5 mg (study II, 74 patients), administered as a single intravenous dose over 15 minutes just before the start of chemotherapy. Results In study I total control of acute symptoms (no nausea and no vomiting) was achieved in, respectively, 66%, 50%, 64% and 50% in the 5-, 10-, 20- and 40-mg groups of patients. A total absence of vomiting alone was seen in, respectively, 71%, 51%, 61% or 58% of patients. None of the differences were statistically significant. In study II there was total acute control in 57% of patients in the 2-mg group and 63% in the 5-mg group (p ─ NS). Total or major control of vomiting (≤2 emetic episodes) was the primary endpoint in study II and was seen in 68% of patients for the 2-mg and 86% for the 5-mg group (p─0.055). In this study failures (> 3 vomiting) were rescued with a second infusion of tropisetron (5-mg fixed dose). Three of 8 rescue infusions administered in the 2-mg group prevented further vomiting whereas none of 5 were successful in the 5-mg group during course 1 of chemotherapy. The most frequently reported adverse effects (over all three courses) were headache (6.0% of 217 patients) hypertension (3.7%) and diarrhoea (2.8%). None of the 25 deaths which occurred during the two studies were attributable to tropisetron. Conclusions Thus, a single dose of tropisetron provides 24-hour protection against cisplatin-induced nausea and vomiting and is well tolerated. These studies do not allow a firm conclusion but suggest that 2 mg may be subtherapeutic and that 5 mg is as effective as higher doses.