Intravenous itasetron: Establishing the effective dose range for the prophylactic control of acute emesis in cancer patients undergoing high-dose cisplatin chemotherapy

Nausea and vomiting induced by chemotherapy are a major cause of distress t o patients and reduce compliance with potentially beneficial treatment. Ita setron hydrochloride is a new 5-hydroxytryptamine(3) (5-HT3) antagonist wit h potent antiemetic properties. It is more potent than ondansetron in anima l models and in early clinical studies it demonstrates a long half-life and does not undergo hepatic biotransformation before elimination, The aim of this open, uncontrolled study was to establish the effective dose range of itasetron hydrochloride given intravenously (i.v.) to patients due to recei ve high-dose cisplatin chemotherapy (50-120 mg/m(2)) for the first time. Th irty-nine patients were enrolled in the trial and received a single i.v, in fusion of itasetron hydrochloride at a dose of 17-280 mu g/kg body weight b efore commencing the cisplatin infusion (median dose 90-110 mg/m(2)), Antie metic protection was demonstrated by doses in the range of 35-280 mu g/kg. The 17 mu g/kg dose was not effective. Treatment failure (>5 emetic episode s/24 hours) was reported in only six (16%) of the 38 evaluable patients ove r all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Phys icians' and patients' assessments of efficacy and tolerability of itasetron hydrochloride were similar, the majority rating the treatment as 'good' or 'very good'. In conclusion, itasetron hydrochloride is effective in the do se range 35-280 mu g/kg in preventing cisplatin-induced emesis. Taken toget her with results from a larger dose-finding study, a dose corresponding to 35 mu g/kg (equivalent to 2.5 mg itasetron, calculated as free base) has be en pursued in Phase III studies with the i.v. formulation.