AN OPEN MULTICENTER STUDY OF TROPISETRON FOR CISPLATIN-INDUCED NAUSEAAND VOMITING

Objectives: (i) To assess the efficacy and tolerability of tropisetron when used for acute and delayed cisplatin-induced emesis. (ii) To inv estigate whether dexamethasone added to tropisetron improves the contr ol of emesis for patients who do not achieve a complete response to tr opisetron alone, (iii) To assess sex of the patient and alcohol intake as prognostic factors for nausea and vomiting. Design: A prospective open label phase II trial over one or two cycles of chemotherapy Data collection was based on observed response and patients' self-reporting . Setting: Twenty Australian tertiary care hospitals in 1994. Patients : 102 male and female patients from 18 to 75 years with histologically confirmed malignancy receiving their first chemotherapy containing gr eater than or equal to 50 mg/m(2) cisplatin. Intervention: In Cycle 1 tropisetron 5 mg was given intravenously before chemotherapy on Day 1, then 5 mg orally before breakfast on Days 2 to 6. In Cycle 2, dexamet hasone 20 mg intravenously on Day 1, then 8 mg orally on Days 2 to 6 c ould be added to tropisetron if a complete antiemetic response had not been achieved in Cycle 1. Main outcome measures: Number of vomiting e pisodes and severity of nausea for 6 days after chemotherapy; severity of side effects; patient satisfaction with chemotherapy treatment; oe stradiol levels in women; and past alcohol consumption in men and wome n. Results: (i) The complete response rate (CR) for acute emesis in Cy cle 1 was 64% (95% confidence interval [CI], 54%-72%), with 84% (95% C I, 76%-90%) having less than or equal to 2 vomits. The CR for delayed emesis was 24% (95% CI, 17%-32%). The CR for acute nausea was 56% (95% CI: 47%-66%), with 97% (95% CI, 91%-99%) having less than or equal to 2 nausea episodes. The CR for delayed nausea was 21% (95% CI, 14%-30% ). Seventy-one patients received Cycle 2. The main side effects were h eadache (20 patients) and constipation (16 patients). The control of a cute emesis was rated as ''good'' or ''very good'' by 68% of investiga tors; 85% rated the tolerability of treatment as ''good'' or ''very go od''. Treatment was rated as ''very satisfactory'' or ''satisfactory'' by 52% of patients. (ii) The CR for acute emesis with dexamethasone a dded was 78% (95% CI, 64%-88%). (iii) Women with lower oestradiol leve ls had better control of emesis, although this difference was not stat istically significant. Chronic alcohol intake and binge drinking were strongly associated with a complete acute antiemetic response. Conclus ions: Tropisetron was effective for acute cisplatin-induced emesis; ad ding dexamethasone enhanced this response. Both single and combined th erapy had less effect on delayed emesis. The impact of alcohol on cont rol of emesis is a chronic rather than acute phenomenon which requires prospective testing.