Efficacy and Safety of Granisetron, a Selective 5-Hydroxytryptamine-3 Receptor Antagonist, in the Prevention of Nausea and Vomiting Induced

Purpse: To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. Patients and Methods: One hundred eighty-four che-motherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 pg/kg) adminis-tered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experi-ences and laboratory parameter changes. Results: After granisetron doses of 5, 10, 20, and 40,/g-71g,a major response (: two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60 % of patients, respectively, and a complete response (no vomiting or retching, and no T HE GOAL OF ACHIEVING effective, well-toler-ated control of cytotoxic-induced emesis was en-hanced by the discovery that an antagonist that acts at the serotonin receptor (5-hydroxytryptamine-3 receptor [5-HT 3]) could prevent nausea and vomiting induced by the highly emetic cytotoxic drug, cisplatin.' " Grani-setron is a potent 5-HT 3 antagonist developed specifi-cally for the prophylaxis of nausea and vomiting associ-ated with emetogenic chemotherapies,4 and is the most selective 5-HT 3 antagonist currently available. 5 Grani-setron has been shown to be effective in the prophylaxi