A dose-finding study of granisetron, a novel antiemetic, in patients receiving high-dose cisplatin. Granisetron Study Group.

In this double-blind study, the efficacy and safety of a single intravenous dose of a novel antiemetic, granisetron, was assessed at two dose levels (40 micrograms/kg and 160 micrograms/kg). A group of 355 patients were given prophylactic granisetron prior to receiving high-dose cisplatin chemotherapy. In the first 24 h, 57% and 59% of patients, respectively, experienced no vomiting and no more than mild nausea. Two further doses of granisetron (40 micrograms/kg) were permitted in the first 24 h to treat any emergent symptoms of nausea and vomiting; 66 patients (39%) in the 40-micrograms/kg treatment group and 56 patients (34%) in the 160-micrograms/kg group received at least one additional dose. Additional treatment with granisetron resulted in resolution or improvement of symptoms in at least 73% of these patients. Over the 7-day study period, 52% of patients in the lower-dose group and 48% in the higher required no further conventional antiemetic therapy. The two different dose levels were equal both in terms in efficacy and safety. Granisetron was well tolerated throughout the dose range of the study [40-240 micrograms kg-1 (24 h)-1]. The commonest adverse event was headache, seen in 14%-16% of patients. In all but one case this resolved spontaneously or responded to simple treatment.