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Investigational New Drugs

, Volume 13, Issue 2, pp 157–162 | Cite as

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. MorganJr.
  • James Raschko
  • George Somlo
  • James H. Doroshow
Phase II Studies

Summary

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.

Keywords

Lung Cancer Congestive Heart Failure Left Ventricular Ejection Fraction Objective Response Reduce Glutathione 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Merry Tetef
    • 1
  • Kim Margolin
    • 1
  • Chul Ahn
    • 2
  • Steven Akman
    • 1
  • Warren Chow
    • 1
  • Lucille Leong
    • 1
  • Robert J. MorganJr.
    • 1
  • James Raschko
    • 1
  • George Somlo
    • 1
  • James H. Doroshow
    • 1
  1. 1.Department of Medical Oncology and Therapeutics ResearchCity of Hope National Medical CenterDuarteUSA
  2. 2.Department of BiostatisticsCity of Hope National Medical CenterDuarteUSA

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