Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

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

  • 16 Accesses

Summary

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 is 3750 mg/m2 every 6 weeks.

This is a preview of subscription content, log in to check access.

References

  1. 1.

    Bernacki RJ, Wilson GL, Mossman BT, Angelino N, Kanter PM, Korytnyk W (1985) Therapeutic and diabetogenic potential of two newly synthesized nitrosoureido sugars. Cancer Res 45: 695–702

  2. 2.

    Brown MB, Engleman L, France JW, Hill MA, Jenrich RI, Toporce JD (1981) BMDP statistical software. University of California, Los Angeles

  3. 3.

    Cowens JW (1984) Preclinical pharmacology of ethyl 6-deoxy-3,6 di-O-methyl-6-(3 methyl-3 nitrosoureido)-α-D-glucofuranoside (CGP 6809) in the rat. Proc AACR 25: 292

  4. 4.

    Cowens JW, Pendyala L, Madajewicz S, Creaven P (1985) Pharmacokinetics of ethyl 6-deoxy-3,6 di-O-methyl-6-(3-methyl-3-nitrosoureido)-α-D-glucofuranoside (CGP 6809). Proc ASCO 4: 47

  5. 5.

    Creaven PJ, Plager JE, Cowens JW, Madajewicz S, Pendyala L, Mittelman A, Petrelli N, Herrera L, Karakousis C, Razack M, Takita H, Huben R, Cushman K (1986) Phase I trial of ethyl 6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)-α-D-glucofuranoside (CGP 6809 EDMN). Proc Am Soc Clin Oncol 5: 36 (141)

  6. 6.

    Kanter PM, Pavelic Z, Bullard GA (1983) Preclinical pharmacological study of CGP 6809: report on therapeutic and toxicological effects. IND application to U. S. Food and Drug Administration

  7. 7.

    Schieweck K, Stanek J, Schmidt-Ruppin H (1982) Effects of a new nitrosoureido-sugar derivative, CGP 6809. Proceedings of the 13th International cancer Congress, p 385

Download references

Author information

Correspondence to Patrick J. Creaven.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Creaven, P.J., Madajewicz, S., Cowens, J.W. et al. 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. 20, 37–40 (1987). https://doi.org/10.1007/BF00252957

Download citation

Keywords

  • Sugar
  • Ethyl
  • Diarrhea
  • Abdominal Pain
  • Partial Response