Phase I clinical trial of ethyl 6-deoxy-3,5-di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809)

Cancer Chemother Pharmacol. 1987;20(1):37-40. doi: 10.1007/BF00252957.

Abstract

A phase I study of single i.v. doses of a new sugar containing nitrosourea 6-deoxy-3,5 di-O-methyl 6-(3 methyl-3-nitrosoureido)-alpha-D-glucofuranoside (CGP 6809, EDMN) has been carried out in 47 patients with advanced solid tumors. Nine dose levels between 200 and 4500 mg/m2 were examined. Nausea and vomiting were seen in most patients but were controlled with antiemetics. Myelosuppression was minimal. The dose-limiting toxicity was hepatotoxicity, occurring early (peak at days 2-4) and resolving rapidly. No cumulative toxicity was seen with an every 6 weeks schedule. Other toxicities were abdominal pain, diarrhea, arm pain, restlessness, and headache. Pharmacokinetic studies in 20 patients using an HPLC assay and in 5 patients using [14C]EDMN showed a short half-life, rapid plasma clearance, rapid metabolism, and minimal excretion of unchanged drug. There was one partial response in a patient with colon carcinoma. The recommended dose for phase II studies in 3750 mg/m2 every 6 weeks.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Chromatography, High Pressure Liquid
  • Clinical Trials as Topic
  • Female
  • Humans
  • Infusions, Intravenous
  • Kinetics
  • Liver Function Tests
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Neoplasms / drug therapy*
  • Nitrosourea Compounds / adverse effects
  • Nitrosourea Compounds / metabolism
  • Nitrosourea Compounds / therapeutic use*
  • Vomiting / chemically induced

Substances

  • Nitrosourea Compounds
  • CGP 6809