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 μg/kg (study 1) and 40–160 μg/kg (study 2) were examined in patients receiving high-dose cisplatin regimens. In study 3, i.v. doses of 40 and 160 μg/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 μg/kg dose compared with 61.5% ( 32 52 ) and 30.8% ( 16 52 ) in the 10 and 2 μg/kg groups, respectively (40 vs. 2 μg/kg; P < 0.001). There were no significant differences between doses of 40 and 160 μg/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 μg/kg prophylactic dose provides optimal control of cytotoxic-induced nausea and vomiting. A simple 3 mg single-dose i.v. regimen (equivalent to 40 μg/kg in a 75 kg person) is recommended for prevention of acute emesis associated with all cytotoxic regimens.
Read full abstract