Tropisetron (Navoban) alone and in combination with dexamethasone in the prevention of chemotherapy-induced emesis: the Nordic experience.

Three Nordic multicenter studies were performed between 1988 and 1992 to evaluate the efficacy of tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland) as an antiemetic agent in patients undergoing various types of chemotherapy. More than 1,050 patients were recruited from cancer centers in Sweden, Finland, and Denmark. In the first two studies, chemotherapy-naive patients were studied for 6-day periods over two consecutive treatment cycles. The first study comparing tropisetron with a metoclopramide cocktail was performed as an open, randomized, multicenter, parallel-group study. All 259 chemotherapy-naive patients received cisplatin > or = 50 mg/m2 on the first day of chemotherapy; other cytostatic agents were allowed on days 1 to 6 of therapy. Patients received either tropisetron or an antiemetic cocktail of metoclopramide, dexamethasone, and lorazepam over the study period. Total control of acute vomiting during the first course of chemotherapy was achieved in 63% of patients in the tropisetron treatment group and in 64% of patients in the antiemetic cocktail group. Acute nausea was prevented completely in 40% of patients in the tropisetron group and in 61% of the metoclopramide cocktail group during course 1 (P < .001). For delayed nausea and vomiting, there were no significant differences between the two antiemetic regimens. Both antiemetic regimens were well tolerated. The second study compared the efficacy of tropisetron plus placebo with tropisetron plus dexamethasone for the prevention of acute and delayed nausea and vomiting during cisplatin-containing chemotherapy in patients not fully controlled by tropisetron monotherapy during course 1. One hundred sixty patients were involved in this double-blind, randomized, placebo-controlled trial. Acute vomiting was completely prevented in 40% of patients treated with tropisetron plus placebo compared with 75% of patients treated with tropisetron plus dexamethasone (P = .001). The results for acute nausea were similar. Delayed vomiting and delayed nausea were completely prevented in significantly more patients receiving the tropisetron-dexamethasone combination than in those receiving the tropisetron-placebo combination (P < .05). Adverse events were reported less frequently in patients receiving tropisetron together with dexamethasone. The third study was an open, nonrandomized multicenter trial designed to investigate the long-term antiemetic effect of tropisetron on various types of chemotherapy and on various types of patients. An interim analysis of this study has been reported previously (Ann Oncol 4:539-542, 1993). Six hundred thirty patients were studied over a mean number of 4.6 courses (range, 1 to 19 courses) of chemotherapy. Each received tropisetron daily on days 1 to 6 of therapy. Complete protection from nausea and vomiting was achieved in 67% of the complete series. The long-term effects of tropisetron therapy remained consistent over 10 consecutive courses of chemotherapy. Tropisetron was more effective during noncisplatin treatment compared with cisplatin treatment; it was also more effective in men and in older patients (> 50 years of age). The most frequent adverse events were headache (18%) and constipation (8%).