A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer

G. M. Tierney, N. R. Griffin, R. C. Stuart, H. Kasem, K. P. Lynch, J. T. Lury, P. D. Brown, A. W. Millar, R. J. C. Steele, S. L. Parsons

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    Abstract

    The aim of this study was to evaluate the safety and tolerability of 4 weeks administration of marimastat, and to seek evidence of biological activity as observed by changes in the endoscopic appearance of the gastric tumours. 35 patients with advanced, inoperable gastric or gastro-oesophageal tumours were recruited. The dose of marimastat was reduced from the starting dose of 50 mg twice daily (6 patients) to 25 mg once daily (29 patients). 31 completed the 28 day study period. Marimastat was generally well tolerated, with the principal treatment-related toxicity being pain and stiffness of the musculoskeletal system. These symptoms occurred more frequently at the higher-dose, and increased to involve a total of 13 patients (37%) with longer-term treatment. The events were usually rapidly reversible on drug discontinuation. 3 patients receiving prolonged treatment experienced more severe symptoms, with the development of skin thickening and contractures in the hands. At endoscopy, 10 patients showed an increased fibrotic cover of the tumour, 8 had decreased haemorrhagic appearance, and in at least 2 cases where comparative tumour histology was assessable, there was evidence of increased stromal fibrotic tissue.
    Original languageEnglish
    Pages (from-to)563-568
    Number of pages6
    JournalEuropean Journal of Cancer
    Volume35
    Issue number4
    DOIs
    Publication statusPublished - 1999

    Keywords

    • Adult
    • Aged
    • Aged, 80 and over
    • Dose-Response Relationship, Drug
    • Enzyme Inhibitors
    • Humans
    • Hydroxamic Acids
    • Metalloendopeptidases
    • Middle Aged
    • Pilot Projects
    • Stomach Neoplasms
    • Treatment Outcome

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  • Cite this

    Tierney, G. M., Griffin, N. R., Stuart, R. C., Kasem, H., Lynch, K. P., Lury, J. T., Brown, P. D., Millar, A. W., Steele, R. J. C., & Parsons, S. L. (1999). A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer. European Journal of Cancer, 35(4), 563-568. https://doi.org/10.1016/S0959-8049(99)00007-6