Phase I trial of 1,2,4-triglycidylurazol (TGU, NSC 332488): a new triepoxide cytostatic agent.
1,2,4-Triglycidylurazol, a new triepoxide derivative, was chosen for phase I trial because of its favorable water solubility, stability and antitumor activity in murine systems. Fifty-seven patients were evaluable. Hematologic toxicity was dose-limiting, with a steep dose-toxicity curve. At 650 mg/m2 2/10 patients developed grade II toxicity. Seventeen patients were treated at 800 mg/m2 and seven developed grade III or IV toxicity according to WHO. Five of these patients had received greater than 3 cytotoxic agents and/or extensive radiotherapy. One toxic death was seen. Cumulative toxicity was observed with respect to hematologic values in a comparison of the first and second courses. Sixteen patients developed phlebitis after injection, not dose-dependent and not dose-limiting. Response was noted in three patients, two non-small cell lung cancers and one bladder cancer. Recommended doses for phase II trials are 800 mg/m2 q 4 weeks for patients who have received less than or equal to 3 cytotoxic agents and 650 mg/m2 q 4 weeks for heavily pretreated patients.