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Dose-finding study of tropisetron in cisplatin-induced nausea and vomiting
S J Van Belle1, L Stamatakis, H Bleiberg
1University Hospital of the VUB, Jette, Belgium.
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 (< or = 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.