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Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience

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Abstract

Malignant gliomas are very difficult neoplasms for clinicians to treat. The reason for this is multifaceted. Many treatments that are effective for systemic cancer are unable to cross the blood-brain barrier and/or have unacceptable systemic toxicities. Consequently, in recent years an effort has been placed on trying to develop innovative local treatments that bypass the blood-brain barrier and allow for direct treatment in the central nervous system (CNS)—interstitial treatment. In this paper, we present our extensive experience in using interstitial chemotherapy as a strategy to treat malignant brain tumors at a single institution (The Johns Hopkins Hospital). We provide a comprehensive summary of our preclinical work on interstitial chemotherapy at the Hunterian Neurosurgery Laboratory, reviewing data on rat, rabbit, and monkey studies. Additionally, we present our clinical experience with randomized placebo-controlled studies for the treatment of malignant gliomas. We compare survival statistics for those patients who received placebo versus Gliadel® as initial therapy (11.6 months vs. 13.9 months, respectively) and at the time of tumor recurrence (23 weeks vs. and 31 weeks, respectively). We also discuss the positive impact of local therapy in avoiding the toxicities associated with systemic treatments. Furthermore, we provide an overview of newer chemotherapeutic agents and other strategies used in interstitial treatment. Finally, we offer insight into some of the lessons we have learned from our unique perspective.

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Acknowledgements

Disclosure: Dr. Henry Brem and the Johns Hopkins University are entitled to a share of royalty by MGI Pharma, Inc. on potential sales of some products that are in development and described in this work. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. Prakash Sampath is a member of the Speakers Bureau for MGI Pharma, Inc., formerly Guildford Pharmaceuticals, Inc.

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Authors and Affiliations

  1. Department of Neurological Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    H. Christopher Lawson, Eileen Bohan, Alessandro Olivi, Jon Weingart, Lawrence Kleinberg & Henry Brem

  2. Department of Radiation Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Alessandro Olivi, Jon Weingart, Lawrence Kleinberg & Henry Brem

  3. Department of Clinical Neurosciences Program in Neurosurgery, Brown Medical School, Rhode Island Hospital, Providence, RI, USA

    Prakash Sampath & Michael C. Park

  4. Department of Neurosurgery, University of Arizona, Tucson, AZ, USA

    Namath Hussain

  5. Roger Williams Hospital, 825 Chalkstone Avenue, Providence, 02908, RI, USA

    Prakash Sampath

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  1. H. Christopher Lawson
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  2. Prakash Sampath
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  3. Eileen Bohan
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  4. Michael C. Park
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  6. Alessandro Olivi
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  9. Henry Brem
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Correspondence to Prakash Sampath.

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Lawson, H.C., Sampath, P., Bohan, E. et al. Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience. J Neurooncol 83, 61–70 (2007). https://doi.org/10.1007/s11060-006-9303-1

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