teroxirone and Hematologic-Diseases

Teroxirone is a novel triepoxide, synthesized as an alkylator and showing a broad spectrum of preclinical activity. It has good cytotoxic activity against sublines of P388 and L1210 leukemias resistant to another alkylating agent, cyclophosphamide. Thirty-six patients received teroxirone as a single iv push for 5 sequential days every 4 weeks. The dose-limiting toxic effects were phlebitis and cutaneous "flare" reactions, with a maximal tolerated dose of 340 mg/m2/day X 5. Nausea, vomiting, and myelosuppression were present but were not dose-limiting at the maximal tolerated dose. This dose would probably be a reasonable dose for phase II trials, but could not be delivered repeatedly without a central line. Since the local reactions were very severe and unique, we believe that studies on the safety of repeated administration via a central line should be completed in animals before trials of systemic therapy in humans begin.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Evaluation; Female; Hematologic Diseases; Humans; Infusions, Parenteral; Kinetics; Male; Middle Aged; Neoplasms; Thrombophlebitis; Triazines