alpha-/beta-Triglycidyl-urazol (TGU, NSC 332488, I.N.N.: ANAXIRONE): a new chemotherapeutic agent.

Triglycidyl-urazol (TGU) was a rational drug development from the original triepoxide triglycidyl-triazinetrione (TGT). It was selected for further studies because of its superior physico-chemical properties as well as its improved therapeutic range in animals. Like the parent compound, TGU exerts antitumour activity in a wide spectrum of experimental tumours, including those resistant to cyclophosphamide. Its biochemical reactivity is very high, a fact which may contribute to its rapid plasma clearance after parenteral administration. Bone marrow suppression constitutes the dose-limiting toxicity in animals and man with a vague suggestion of cumulative effects. Other toxicities are generally mild and rapidly reversible. The new chemical structure, its reproducible experimental antitumour activity combined with an acceptable and manageable toxicology warranted the introduction of the compound into the clinic. Phase I studies in patients have largely confirmed the predicted toxicities and probable antitumour activity in man (7, 12, 13). Consequently, clinical phase II studies in various tumour types are now under way.