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

Merry Tetef, Kim Margolin, Chul Ahn, Steven Akman, Warren Chow, Paul Coluzzi, Lucille Leong, Robert J. Morgan, James Raschko, Stephen Shibata, George Somlo, James H. Doroshow

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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 left0ventricular 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.

Original languageEnglish (US)
Pages (from-to)103-106
Number of pages4
JournalJournal of Cancer Research and Clinical Oncology
Volume121
Issue number2
DOIs
StatePublished - Feb 1 1995

Keywords

  • Menadione Gastrointestinal cancer
  • Mitomycin C

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tetef, M., Margolin, K., Ahn, C., Akman, S., Chow, W., Coluzzi, P., Leong, L., Morgan, R. J., Raschko, J., Shibata, S., Somlo, G., & Doroshow, J. H. (1995). Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. Journal of Cancer Research and Clinical Oncology, 121(2), 103-106. https://doi.org/10.1007/BF01202221