Intravenous granisetron--establishing the optimal dose. The Granisetron Study Group

Three double-blind, dose-ranging studies, involving 996 chemotherapy-naive patients, were conducted to determine the optimal prophylactic dose of intravenous (i.v.) granisetron for prevention of cytotoxic-induced emesis. The antiemetic efficacy of prophylactic i.v. granisetron doses ranging from 2-40 micrograms/kg (study 1) and 40-160 micrograms/kg (study 2) were examined in patients receiving high-dose cisplatin regimens. In study 3, i.v. doses of 40 and 160 micrograms/kg were compared in patients receiving other emetogenic cytotoxic therapies. In study 1, 67.9% (36/53) of patients were complete responders at 24 h following the 40 micrograms/kg dose compared with 61.5% (32/52) and 30.8% (16/52) in the 10 and 2 micrograms/kg groups, respectively (40 vs. 2 micrograms/kg; P less than 0.001). There were no significant differences between doses of 40 and 160 micrograms/kg in any efficacy parameter in Studies 2 and 3. Granisetron was well tolerated across the dose range examined and no dose-related toxicity was observed. In conclusion, a single 40 micrograms/kg prophylactic dose provides optimal control of cytotoxic-induced nausea and vomiting. A simple 3 mg single-dose i.v. regimen (equivalent to 40 micrograms/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.