PHASE-I TRIAL AND PHARMACOKINETICS OF AZIRIDINYLBENZOQUINONE (NSC-182986) IN HUMANS

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  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (4) , 1582-1586
Abstract
2,5-Diaziridinyl-3,6-(carboethoxyamino)-1,4-benzoquinone (AZQ) is a rationally designed antitumor agent which possesses sufficient lipid solubility to allow CNS penetration and adequate aqueous solubility for drug formulation and administration. A Phase I trial of AZQ was conducted in 40 previously treated patients with advanced cancer. The drug was given as a 15-min i.v. infusion on Days 1 and 8 of a 28-day cycle. Seven dose levels ranging from 1-25 mg/m2 were studied with 3-11 patients treated at each level. Sixty-nine evaluable cycles of AZQ were administered. The major toxicity was myelosuppression, with the nadir in white blood cells and/or platelet count occurring at Days 15-20 of the cycle and 1st appearing at doses > 10 mg/m2. The highest tolerated dose was 20 mg/m2; this dose is recommended for Phase II trials. Other toxicities were mild nausea, slight alopecia and anemia. Plasma pharmacokinetics was studied in 11 patients by a high-performance liquid chromatography assay. Plasma decay curves could be fitted to a 2-compartment open model of drug disappearance with a dose-independent terminal half-life of 33.3 .+-. 4.5 (SD) min. CSF AZQ levels were determined in 3 patients and revealed readily detectable levels of AZQ.

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