EFFICACY AND SAFETY OF DIFFERENT DOSES OF GRANISETRON FOR THE PROPHYLAXIS OF CISPLATIN-INDUCED EMESIS

The purpose of this study was to evaluate the efficacy and safety of f our different doses of granisetron when administered as a single intra venous (i.v.) dose for prophylaxis of cisplatin-induced emesis in a mu lticenter, randomized, parallel-group, double-blind investigation. A t otal of 353 chemotherapy-naive patients were enrolled, stratified acco rding to cisplatin dose (moderate dose: 50-80 mg/m(2), n = 169; high d ose: 81-120 mg/m(2), n = 184) and randomized to one of four granisetro n doses: 5, 10, 20, or 40 mu g/kg. Control of emesis was evaluated by the percentages of patients attaining complete response (no vomiting o r retching, and no rescue medication) and major response (less than or equal to 2 episodes of vomiting or retching, and no rescue medication ). Patients were assessed on an inpatient basis for 18-24 h. Safety an alyses consisted of adverse events and laboratory parameter changes. C omplete response rates over 24 h after chemotherapy were 23%, 48%, 48% , and 44% for granisetron doses of 5, 10, 20, and 40 mu g/kg, respecti vely, in the combined patient population (P=0.011 for linear trend); 2 9%, 56%, 58%, and 41%, respectively, in the moderate-dose cisplatin st ratum (P=0.278 for linear trend); and 18%, 41%, 40%, and 47%, respecti vely, in the high-dose cisplatin stratum (P=0.011 for linear trend). T ransient headache was the most frequently reported adverse event (19%) . There was no evidence of association between increased dose and head ache. A single 10-, 20- or 40-mu g/kg dose of granisetron is comparabl y effective in controlling nausea and vomiting associated with moderat e- or high-dose cisplatin chemotherapy. Granisetron was safe and well tolerated at all doses.