Phase I trial of α-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) in patients with advanced prostatic cancer Academic Article Article uri icon

Overview

MeSH Major

  • Cystadenocarcinoma
  • Prostatic Neoplasms

abstract

  • Both alpha-difluoromethyl ornithine (DFMO) and methylglyoxal bis (guanylhydrazone) (MGBG) inhibit sequential enzymatic reactions in the pathway of polyamine biosynthesis. Since polyamines may be important factors in proliferation of cancer cells and DFMO combined with MGBG has shown synergistic cytotoxicity in an experimental prostatic tumor, we evaluated these agents in phase I clinical trial involving 5 patients with advanced, hormone-resistant prostatic cancer. Toxic reaction to combined DFMO and MGBG was dose-related and included nausea, fatigue, and diarrhea especially with the higher doses of MGBG. No therapeutic responses of significance were seen, but toxicity precluded adequate evaluation. Future Phase II studies of combined DFMO and MGBG should employ low, nontoxic doses of MGBG combined with evaluation of polyamine levels and inhibition of polyamine enzymatic activity to minimize toxicity.

publication date

  • January 1986

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1016/0090-4295(86)90154-8

PubMed ID

  • 3097903

Additional Document Info

start page

  • 508

end page

  • 11

volume

  • 28

number

  • 6