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[Cancer Research 46, 3569-3573, July 1, 1986]
© 1986 American Association for Cancer Research
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Protective Effect of Sodium-2-mercaptoethanesulfonate on the Gastrointestinal Toxicity and Lethality of cis-Diamminedichloroplatinum

Simon G. Allan1, John F. Smyth, Frances G. Hay, Robert C. F. Leonard and C. Roland Wolf2

Imperial Cancer Research Fund, Medical Oncology Unit [S. G. A., C. R. W.], and University Department of Clinical Oncology [J. F. S., F. G. H., R. C. F. L.], Western General Hospital, Edinburgh EH4 2XU, Scotland

cis-Diamminedichloroplatinum (cis-platinum) is an effective and widely used antitumor drug. Patients receiving cis-platinum, however, experience very profound and long lasting gastrointestinal symptoms. The role of intestinal mucosal toxicity in the pathogenesis of these symptoms is unclear. In this study we have investigated the thiolcontaining compound mesna (sodium-2-mercaptoethanesulfonate) as a potential antidote to cis-platinum-induced gastrointestinal tract damage.

In mice, mesna caused a significant reduction in the gastrointestinal toxicity of cis-platinum assessed by electron microscopy, villus recovery rate, and by disaccharidase estimations. Mesna also significantly reduced serum creatinine levels following cis-platinum. Administration of mesna prior (or immediately following) a 67% lethal dose of cis-platinum protected 87–100% of the animals from the lethal effects.

The antitumor efficacy of cis-platinum in L1210 leukemia bearing mice was not affected by coadministration of mesna indicating that the protective effect may be tissue specific. In addition this finding indicates that mesna has potential as an agent which may improve the therapeutic index of cis-platinum in clinical practice.

1 To whom requests for reprints should be addressed.

2 Present address: Imperial Cancer Research Fund, Laboratory of Molecular Pharmacology and Drug Metabolism, Department of Biochemistry, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, Scotland, United Kingdom.

Received 7/29/85. Revised 12/27/85. Revised 3/17/86. Accepted 3/20/86.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1986 by the American Association for Cancer Research.