Phase I study of triglycidylurazol given on a 5-day i.v. schedule

Triglycidylurazol is a teroxirone derivative proposed for clinical trials on the basis of a broad spectrum of activity against murine tumors and a reduced potential for toxic manifestations at the injection site as compared to the parent compound. This phase I trial was designed to define the maximum tolerated dose of triglycidylurazol given by iv bolus on a 5-day schedule. Twenty-eight adult patients with a variety of solid tumors were entered. Their median performance status was 2 (range, 0-3), and most had received prior radiotherapy, chemotherapy, or both. A median of one course (range, one to four) was administered, for a total of 47 courses. Doses were escalated from 6 to 250 mg/m2/day. Leukopenia and thrombocytopenia were dose-related and -limiting, with a strong suggestion of increased myelosuppression with repeated courses. Nonhematologic toxic effects were generally mild to moderate. Nausea and vomiting were experienced by most patients. Local toxic effects consisting of venous discoloration, phlebitis, and/or sloughing were encountered in about one-half of the patients. Possible drug-related impairments in liver function were noted in three patients. Negligible alopecia and fatigue were also observed. Antitumor effect was detected in one patient with adenocarcinoma of unknown origin. A dose of 200 mg/m2/day for 5 consecutive days may be recommended for phase II trials.