A clinical and pharmacokinetic phase I study of 1,2,4-triglycidylurazol (TGU, NSC 332488)

Eur J Cancer Clin Oncol. 1986 Nov;22(11):1325-9. doi: 10.1016/0277-5379(86)90140-9.

Abstract

Twenty-six patients with advanced malignancies received TGU given as an intravenous (i.v.) bolus in physiological saline at 3 weekly intervals. The starting dose was 30 mg/m2 with standard graded escalations to 900 mg/m2. Myelosuppression occurred at 800 mg/m2, with a mean nadir of 2.0 +/- 0.8 X 10(9)/l and a mean nadir platelet count of 41 +/- 31 X 10(9)/l. At 800 or 900 mg/m2 nausea and vomiting was WHO grade 0 in 5, grade I in 6, grade II in 11 and grade III in 10 courses of therapy. Alopecia did not occur. TGU was given by i.v. infusion at 800 mg/m2 in 2 patients, both of whom developed severe thrombophlebitis. Five patients given TGU by i.v. bolus developed mild phlebitis. No renal, hepatic or cardiac toxicity was noted. Two patients had partial responses; both had adenocarcinoma of unknown primary origin, one of whom had been resistant to prior therapy with FAM. An HPLC analytical method was developed with a sensitivity of 250 ng/ml. The data from 7 patients studied best fit a one compartment pharmacokinetic model with an exponential decay and a t1/2 of only 2.1 min. In conclusion, the dose limiting toxicity of TGU appears to be myelosuppression and we would recommend a dose of 800 mg/m2 given as an intravenous bolus every 4 weeks for future phase II trials.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Drug Evaluation
  • Female
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Triazoles / adverse effects
  • Triazoles / metabolism
  • Triazoles / therapeutic use*

Substances

  • Antineoplastic Agents
  • Triazoles
  • anaxirone