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Neurotoxicity of Biologically Targeted Agents in Pediatric Cancer Trials

  • Elizabeth M. Wells
    Affiliations
    Brain Tumor Institute, Children’s National Medical Center, Washington, DC

    Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Washington, DC

    Department of Neurology and Pediatrics, George Washington University, Washington, DC
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  • Amulya A. Nageswara Rao
    Affiliations
    Brain Tumor Institute, Children’s National Medical Center, Washington, DC

    Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Washington, DC

    Department of Neurology and Pediatrics, George Washington University, Washington, DC

    Division of Pediatric Hematology/Oncology, Department of Pediatrics and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota
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  • Joseph Scafidi
    Affiliations
    Brain Tumor Institute, Children’s National Medical Center, Washington, DC

    Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Washington, DC

    Department of Neurology and Pediatrics, George Washington University, Washington, DC
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  • Roger J. Packer
    Correspondence
    Communications should be addressed to: Dr. Packer; Department of Neurology; Children’s National Medical Center; 111 Michigan Avenue NW; Washington, DC 20010.
    Affiliations
    Brain Tumor Institute, Children’s National Medical Center, Washington, DC

    Center for Neuroscience and Behavioral Medicine, Children’s National Medical Center, Washington, DC

    Department of Neurology and Pediatrics, George Washington University, Washington, DC
    Search for articles by this author

      Abstract

      Biologically targeted agents offer the promise of delivering specific anticancer effects while limiting damage to healthy tissue, including the central and peripheral nervous systems. During the past 5-10 years, these agents were examined in preclinical and adult clinical trials, and are used with increasing frequency in children with cancer. This review evaluates current knowledge about neurotoxicity from biologically targeted anticancer agents, particularly those in pediatric clinical trials. For each drug, neurotoxicity data are reviewed in adult (particularly studies of brain tumors) and pediatric studies when available. Overall, these agents are well tolerated, with few serious neurotoxic effects. Data from younger patients are limited, and more neurotoxicity may occur in the pediatric population because these agents target pathways that control not only tumorigenesis but also neural maturation. Further investigation is needed into long-term neurologic effects, particularly in children.
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