DOSE-RANGING ANTIEMETIC EVALUATION OF THE SEROTONIN ANTAGONIST RG-12915 IN PATIENTS RECEIVING ANTICANCER CHEMOTHERAPY

Background. RG 12915 is a potent, selective 5-HT3 receptor antagonist with a biologic half-life of 11-20 hours. RG 12915 prevents cisplatin- induced emesis in ferrets at doses of 0.03 mg/kg. Animal toxicology st udies permitted safe testing in humans at doses of up to 2.0 mg/kg. Th is dose-ranging trial of intravenous RG 12915 was performed to determi ne the optimal dosage and adverse effects and to observe for antiemeti c effects in patients receiving anticancer chemotherapy. Methods. Twen ty-six patients receiving chemotherapy likely to cause vomiting receiv ed a single intravenous dose of RG 12915 at a rate of 3 ml/minute begi nning 60 minutes before chemotherapy. Four dose levels were explored: 0.25, 0.50, 1.0, and 2.0 mg/kg. Results. No dose-limiting toxicities w ere observed. All adverse effects were mild and transient and included discomfort at the infusion site, hyperglycemia, headache, serum aspar tate transaminase (AST) and alanine transaminase (ALT) elevations, and sedation. Antiemetic efficacy was seen in patients receiving cisplati n al doses of greater than or equal to 100 Mg/m2. Conclusion. RG 12915 can be administered safely at the dose levels explored. Single intrav enous doses of RG 12915 prevented or lessened emesis caused by chemoth erapy, including cisplatin given at doses of greater than or equal to 100 mg/m2. RG 12915 warrants further testing. Of the doses tested, the 2.0 mg/kg dose is the most appropriate for further exploration.