Phase I and pharmacokinetic studies of DON

Cancer Treat Rep. Nov-Dec 1981;65(11-12):1031-6.


DON, a glutamine antagonist, was administered iv to 26 patients with advanced cancer either once every 3 wks or daily for 3 days every 3 wks to determine toxicity and to look for evidence of therapeutic effect. Total doses ranged from 150 to 600 mg/m2. The single-day schedule produced intolerable nausea and vomiting and no evidence of cytotoxicity at 450-550 mg/m2 given over 10 mins or over 4 hrs. On the 3-day schedule, patients had tolerable gastrointestinal toxic effects at total doses up to 480 mg/m2 given in three equally divided doses by 10-min infusion. This dose also produced cytotoxic activity manifested as transient mild leukopenia and, rarely, thrombocytopenia. No objective responses were seen. Analysis of the plasma elimination of DON demonstrated dose-dependent pharmacokinetic behavior. The parent compound was not detectable in the urine of any patient, indicating extensive metabolism of the drug.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Azo Compounds / administration & dosage*
  • Diazooxonorleucine / administration & dosage*
  • Diazooxonorleucine / adverse effects
  • Diazooxonorleucine / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Evaluation
  • Female
  • Half-Life
  • Humans
  • Infusions, Parenteral
  • Injections, Intravenous
  • Male
  • Neoplasms / drug therapy*
  • Vomiting / chemically induced


  • Azo Compounds
  • Diazooxonorleucine