title: Intravenous itasetron: establishing the effective dose range for the prophylactic control of acute emesis in cancer patients undergoing high-dose cisplatin chemotherapy.
abstract: Nausea and vomiting induced by chemotherapy are a major cause of distress to patients and reduce compliance with potentially beneficial treatment. Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist with potent antiemetic properties. It is more potent than ondansetron in animal 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 receive high-dose cisplatin chemotherapy (50-120 mg/m2) for the first time. Thirty-nine patients were enrolled in the trial and received a single i.v. infusion of itasetron hydrochloride at a dose of 17-280 microg/kg body weight before commencing the cisplatin infusion (median dose 90-110 mg/m2). Antiemetic protection was demonstrated by doses in the range of 35-280 microg/kg. The 17 microg/kg dose was not effective. Treatment failure (>5 emetic episodes/24 hours) was reported in only six (16%) of the 38 evaluable patients over all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Physicians' 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 dose range 35-280 microg/kg in preventing cisplatin-induced emesis. Taken together with results from a larger dose-finding study, a dose corresponding to 35 microg/kg (equivalent to 2.5 mg itasetron, calculated as free base) has been pursued in Phase III studies with the i.v. formulation.
authors.affiliation: Policlinico Monteluce, Perugia, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Patoia
authors.forename: A
authors.initials: A
authors.lastname: Del Favero
authors.forename: A
authors.initials: A
authors.lastname: Giglietti
authors.forename: P
authors.initials: P
authors.lastname: Malacarne
authors.forename: D
authors.initials: D
authors.lastname: Donati
authors.forename: M
authors.initials: M
authors.lastname: Indelli
authors.forename: G
authors.initials: G
authors.lastname: Bensi
authors.forename: M A
authors.initials: MA
authors.lastname: Palladino
authors.forename: P
authors.initials: P
authors.lastname: Cigarini
authors.forename: R
authors.initials: R
authors.lastname: Kempe
authors.forename: T
authors.initials: T
authors.lastname: Voigt
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001562:Benzimidazoles / Q000008:administration & dosage*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; C070191:itasetron; D002945:Cisplatin