teroxirone and Leukopenia

Two schedules of teroxirone, a triazine triepoxide, were evaluated in a phase I study. Twenty-six patients were treated on 1 day every 5 weeks at doses of 36-2250 mg/m2. At doses greater than or equal to 1500 mg/m2, severe thrombophlebitis was seen without cytotoxic effect, and this schedule was closed. Twenty-seven patients were treated on 5 days every 5 weeks at daily doses of 16-450 mg/m2. Mild thrombophlebitis and moderate leukopenia were encountered. For phase II studies, a dose of 375 mg/m2 X 5 every 5 weeks is recommended. Pharmacologic studies showed rapid plasma elimination, which suggests the agent's possible usefulness for regional infusion.

Topics: Antineoplastic Agents; Drug Administration Schedule; Drug Evaluation; Humans; Leukopenia; Neoplasms; Thrombophlebitis; Triazines

alpha-1,3,5-Triglycidyl-s-triazinetrione (TGT) is a triepoxide derivative with alkylating properties discovered by random screening. TGT has been found to be active against a wide variety of murine tumors, including a P388 subline resistant to cyclophosphamide. The starting dose in this phase-I study was 30 mg/m2 as a single dose IV, repeated every 3-4 weeks, increasing up to 2,700 mg/m2. Severe dose-limiting toxicity took the form of phlebitis becoming apparent a few days after treatment. This was initially seen at the 480 mg/m2 dose level, and was observed with increasing frequency and intensity at higher dose levels. Leukopenia occurred regularly at dose levels above 1,800 mg/m2 and resulted in life-threatening leukopenia in one patient, and in a toxic death at 2,700 mg/m2 in another patient. Other toxic side-effects included moderate reversible thrombocytopenia, nausea, and vomiting. It is recommended that further trials with TGT await the development of more water-soluble formulations or of other triepoxide derivatives.

Topics: Adult; Aged; Antineoplastic Agents; Drug Evaluation; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasms; Triazines; Vomiting

Topics: Adult; Aged; Alopecia; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Evaluation; Female; Humans; Infusions, Parenteral; Leukopenia; Male; Middle Aged; Nausea; Neoplasms; Thrombophlebitis; Triazines; Vomiting