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

Publication ,  Journal Article
Tetef, M; Margolin, K; Ahn, C; Akman, S; Chow, W; Coluzzi, P; Leong, L; Morgan, RJ; Raschko, J; Shibata, S
Published in: J Cancer Res Clin Oncol
1995

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.

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Published In

J Cancer Res Clin Oncol

DOI

ISSN

0171-5216

Publication Date

1995

Volume

121

Issue

2

Start / End Page

103 / 106

Location

Germany

Related Subject Headings

  • Vitamin K
  • Oncology & Carcinogenesis
  • Mitomycin
  • Middle Aged
  • Male
  • Humans
  • Gastrointestinal Neoplasms
  • Female
  • Antineoplastic Combined Chemotherapy Protocols
  • Aged
 

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Tetef, M., Margolin, K., Ahn, C., Akman, S., Chow, W., Coluzzi, P., … Shibata, S. (1995). Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. J Cancer Res Clin Oncol, 121(2), 103–106. https://doi.org/10.1007/BF01202221
Tetef, M., K. Margolin, C. Ahn, S. Akman, W. Chow, P. Coluzzi, L. Leong, R. J. Morgan, J. Raschko, and S. Shibata. “Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.J Cancer Res Clin Oncol 121, no. 2 (1995): 103–6. https://doi.org/10.1007/BF01202221.
Tetef M, Margolin K, Ahn C, Akman S, Chow W, Coluzzi P, et al. Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. J Cancer Res Clin Oncol. 1995;121(2):103–6.
Tetef, M., et al. “Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial.J Cancer Res Clin Oncol, vol. 121, no. 2, 1995, pp. 103–06. Pubmed, doi:10.1007/BF01202221.
Tetef M, Margolin K, Ahn C, Akman S, Chow W, Coluzzi P, Leong L, Morgan RJ, Raschko J, Shibata S. Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. J Cancer Res Clin Oncol. 1995;121(2):103–106.
Journal cover image

Published In

J Cancer Res Clin Oncol

DOI

ISSN

0171-5216

Publication Date

1995

Volume

121

Issue

2

Start / End Page

103 / 106

Location

Germany

Related Subject Headings

  • Vitamin K
  • Oncology & Carcinogenesis
  • Mitomycin
  • Middle Aged
  • Male
  • Humans
  • Gastrointestinal Neoplasms
  • Female
  • Antineoplastic Combined Chemotherapy Protocols
  • Aged