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Direct delivery of platinum-based antineoplastics to the central nervous system: a toxicity and ultrastructural study

  • Original Articles
  • Platinum Drugs, Carcinomatous Meningitis, Inthrathecal Therapy
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Summary

Platinum drugs are playing an increasingly major role in cancer treatment, but systemic administration of these agents has resulted in significant toxicity. To examine the effects of cisplatin and two newer agents, inprolatin and carboplatin, we injected the agents directly into the cerebrospinal fluid of rats and found that neurotoxic reactions resulted from doses of cisplatin (10 nmol) much lower than those of iproplatin (40 nmol) or carboplatin (80 nmol). Moreover, central nervous system tissue appeared to be less adversely affected by direct exposure to carboplatin since chronic toxicity was not observed in any of the animals receiving carboplatin until a lethal dose was reached. Furthermore, only the animals receiving cisplatin showed histologic damage in their spinal cords, and ultrastructural studies confirmed and while significant abnormalities were observed in the spinal cords of rats receiving 40 nmol cisplatin, no architectural changes were detected in the spinal cords of animals receiving 240 nmol carboplatin. We conclude that platinum drugs can be delivered intrathecally to achieve a much greater concentration of active drug than can be achieved by intravenous administration and that carboplatin appears to be the most suitable platinum-based drug for use in systems delivering drugs directly to the brain and spinal cord.

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Author information

Author notes

  1. Mark Gilbert

    Present address: Department of Medicine, Montefiore University Hospital, 15213, Pittsburgh, PA, USA

  2. Kimberly L. Duncan

    Present address: Laboratory of Biological Chemistry, National Cancer Institute, Bldg 37, Rm. 5D02, 20892, Bethesda, MD, USA

  3. Brian Corden

    Present address: Department of Pediatrics, Emory University, 30322, Atlanta, GA, USA

  4. Doris Lenartz

    Present address: Neurochirurgische Klinik, Krankenanstalten der Stadt Köln, Krankenhaus Merheim, D-5000, Köln 91-den, Germany

Authors and Affiliations

  1. Department of Neurology, Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland, USA

    Mark Gilbert

  2. Department of Oncology, Johns Hopkins University School of Medicine, 21205, Baltimore, Maryland, USA

    Kimberly L. Duncan, Brian Corden & Henry Brem

  3. Department of Neurosurgery, Johns Hopkins Hospital/Meyer, 7-113, 600 N. Wolfe Street, 21205, Baltimore, MD, USA

    Alessandro Olivi, Doris Lenartz & Henry Brem

Authors
  1. Alessandro Olivi
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  2. Mark Gilbert
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  5. Doris Lenartz
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  6. Henry Brem
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Olivi, A., Gilbert, M., Duncan, K.L. et al. Direct delivery of platinum-based antineoplastics to the central nervous system: a toxicity and ultrastructural study. Cancer Chemother. Pharmacol. 31, 449–454 (1993). https://doi.org/10.1007/BF00685034

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  • DOI: https://doi.org/10.1007/BF00685034

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