Down-regulation of tumor necrosis factor expression by pentoxifylline in cancer patients: A pilot study (original) (raw)

Abstract

The wasting syndrome (cachexia) characterized by anorexia, malaise, and weight loss is observed in many patients with cancer or chronic infection. The excessive levels of tumor necrosis factor-α (TNF)/cachectin reported in 50% of cancer patients exhibiting clinically active disease may therefore mediate, at least in part, the cachexia associated with malignancy. Pentoxifylline, a substituted methylxanthine approved for treatment of intermittent claudication, has been shown in preclinical studies to down-regulate TNF RNA expression as well as TNF activity. We report that pentoxifylline suppressed TNF RNA levels on all three occasions in patients with initially elevated levels of TNF RNA. Pentoxifylline did not suppress TNF RNA to subnormal levels in all five patients with initially normal TNF RNA levels. Four patients reported an increased sense of well-being, improved appetite and ability to perform the activities of daily living. Two of these five patients with normal TNF levels each had a weight gain of more than 5% after 3 weeks of pentoxifylline therapy suggesting that, although TNF may be important in the pathogenesis of cancer cachexia, other anorexia-producing cytokines that are potentially affected by pentoxifylline may also be involved. No severe adverse effects were observed. Taken together these findings suggest that pentoxifylline can down-regulate TNF expression and improve the sense of well-being in cancer patients. A larger study with a randomized, double-blind, placebo-controlled design and more sophisticated estimates of quality of life will be needed to confirm these observations.

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Authors and Affiliations

  1. Division of Cell Growth and Regulation, Department of Biological Chemistry and Molecular Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, D810a, 02115, Boston, MA, USA
    Bruce J. Dezube, Judith L. Fridovich-Keil, Judy Allen-Ryan & Arthur B. Pardee
  2. Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, 02115, Boston, MA, USA
    Bruce J. Dezube & Matthew L. Sherman
  3. Division of Medical Oncology, Department of Medicine, Beth Israel Hospital, Harvard Medical School, 02215, Boston, MA, USA
    Bruce J. Dezube

Authors

  1. Bruce J. Dezube
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  2. Matthew L. Sherman
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  3. Judith L. Fridovich-Keil
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  4. Judy Allen-Ryan
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  5. Arthur B. Pardee
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Additional information

This study was supported in part by a grant from Hoechst-Roussel Pharmaceuticals Inc., Somerville, N. J. to Dr. Dezube and by a fellowship from Aid for Cancer Research of Boston, Mass., to Dr. Fridovich-Keil. Part of this work has been presented at a workshop: Pentoxifylline, leukocytes and cytokines, held in Scottsdale, Arizona, 8–10 March 1991

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Dezube, B.J., Sherman, M.L., Fridovich-Keil, J.L. et al. Down-regulation of tumor necrosis factor expression by pentoxifylline in cancer patients: A pilot study.Cancer Immunol Immunother 36, 57–60 (1993). https://doi.org/10.1007/BF01789132

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