Phase I trial of teroxirone.
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.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013924:Thrombophlebitis / Q000139:chemically induced; D014227:Triazines / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D014227:Triazines; C028786:teroxirone