Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.

Journal Article (Clinical Trial;Journal Article)

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.

Full Text

Duke Authors

Cited Authors

  • Tetef, M; Margolin, K; Ahn, C; Akman, S; Chow, W; Coluzzi, P; Leong, L; Morgan, RJ; Raschko, J; Shibata, S

Published Date

  • 1995

Published In

Volume / Issue

  • 121 / 2

Start / End Page

  • 103 - 106

PubMed ID

  • 7883772

International Standard Serial Number (ISSN)

  • 0171-5216

Digital Object Identifier (DOI)

  • 10.1007/BF01202221


  • eng

Conference Location

  • Germany