Mitomycin C and menadione for the treatment of lung cancer: a phase II trial

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

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48 Scopus citations

Abstract

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (iv) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 iv bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), 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 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regressions fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.

Original languageEnglish (US)
Pages (from-to)157-162
Number of pages6
JournalInvestigational New Drugs
Volume13
Issue number2
DOIs
StatePublished - Jun 1 1995

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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    Tetef, M., Margolin, K., Ahn, C., Akman, S., Chow, W., Leong, L., Morgan, R. J., Raschko, J., Somlo, G., & Doroshow, J. H. (1995). Mitomycin C and menadione for the treatment of lung cancer: a phase II trial. Investigational New Drugs, 13(2), 157-162. https://doi.org/10.1007/BF00872865