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Toxicity profile of delayed high dose sodium thiosulfate in children treated with carboplatin in conjunction with blood-brain-barrier disruption

Authors

  • Edward A. Neuwelt MD,

    Corresponding author
    1. Department of Neurology, Oregon Health & Science University Portland, Portland, Oregon
    2. Department of Neurosurgery, Oregon Health & Science University Portland, Portland, Oregon
    3. Veterans Administration Medical Center, Portland, Oregon
    • Blood-Brain Barrier and Neuro-oncology Program, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, L603, Portland, Oregon 97239.
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  • Kristin Gilmer-Knight MS,

    1. Department of Pediatric Audiology, Oregon Health & Science University Portland, Portland, Oregon
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  • Cynthia Lacy RN,

    1. Department of Neurology, Oregon Health & Science University Portland, Portland, Oregon
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  • H. Stacy Nicholson MD, MPH,

    1. Department of Pediatrics, Oregon Health & Science University Portland, Portland, Oregon
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  • Dale F. Kraemer PhD,

    1. Department of Pharmacy Practice, Oregon State University, Portland, Oregon
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  • Nancy D. Doolittle RN, PhD,

    1. Department of Neurology, Oregon Health & Science University Portland, Portland, Oregon
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  • Gregory W. Hornig MD,

    1. Section of Neurosurgery, Childrens Mercy Hospital, Kansas City, Missouri
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  • Leslie L. Muldoon PhD

    1. Department of Neurology, Oregon Health & Science University Portland, Portland, Oregon
    2. Department of Cell and Developmental Biology, Oregon Health & Science University Portland, Portland, Oregon
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  • Dr. Neuwelt, Dr. Muldoon, Oregon Health & Science University, Portland Veterans Affairs Medical Centre and the Department of Veterans Affairs have significant financial interests in Adherex Technology, Inc., a company that may have a commercial interest in the results of this research and technology. The potential conflict of interest has been reviewed and a management plan has been approved by the Oregon Health & Science University and the Portland Veterans Affairs Medical Center Conflict of Interest in Research Committee.

Abstract

Purpose

To assess the safety of delayed high dose intravenous (i.v.) sodium thiosulfate (STS) in a case series of 12 children with malignant brain tumors who were treated with intraarterial (i.a.) carboplatin in conjunction with blood-brain-barrier disruption (BBBD).

Methods

Twelve children ages 17 months–12 years underwent a total of 132 BBBD chemotherapy treatments and also received delayed high dose STS (i.v.). Dose 1 of STS (10–16 g/m2) was administered 2 or 4 hr after carboplatin, and a second STS dose was administered 4 hr after dose 1 if the child had impaired baseline hearing. Toxicity data were graded in accordance with the National Cancer Institute Common Toxicity Criteria (Version 2). Audiologic monitoring to evaluate the otoprotective potential of STS was performed on 11 children. Ototoxicity was defined in accordance with the American Speech-Language-Hearing Association (ASHA) criteria. Baseline and end of treatment hearing status were graded using Brock's criteria.

Results

Nausea and vomiting were well controlled with anti-emetics administered approximately 30 min prior to STS infusion. Analogous to results in adult patients, there was mild transient hypernatremia and a trend for improved protection from ototoxicity in children who received STS delayed to 4 hr post-treatment versus 2 hr. Tumor responses were seen in heavily pre-treated patients with relatively chemo-resistant tumors, suggesting that STS did not protect the tumor from platinum cytotoxicity.

Conclusion

High dose STS is well tolerated in children under 12 years of age. Further studies of STS in children are warranted to assess otoprotection and the impact of STS on platinum mediated efficacy. © 2005 Wiley-Liss, Inc.

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