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New therapeutic approaches for brainstem tumors: a comparison of delivery routes using nanoliposomal irinotecan in an animal model

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Abstract

Despite the advances in imaging, surgery and radiotherapy, the majority of patients with brainstem gliomas die within 2 years after initial diagnosis. Factors that contribute to the dismal prognosis of these patients include the infiltrative nature and anatomic location in an eloquent area of the brain, which prevents total surgical resection and the presence of the blood–brain barrier (BBB), which reduces the distribution of systemically administered agents. The development of new therapeutic approaches which can circumvent the BBB is a potential path to improve outcomes for these children. Convection-enhanced delivery (CED) and intranasal delivery (IND) are strategies that permit direct drug delivery into the central nervous system and are an alternative to intravenous injection (IV). We treated rats bearing human brainstem tumor xenografts with nanoliposomal irinotecan (CPT-11) using CED, IND, and IV. A single treatment of CED irinotecan had a similar effect on overall survival as multiple treatments by IV route. IND CPT-11 showed significantly increased survival of animals with brainstem tumors, and demonstrated the promise of this non-invasive approach of drug delivery bypassing the BBB when combined with nanoliposomal chemotherapy. Our results indicated that using CED and IND of nanoliposomal therapy increase likelihood of practical therapeutic approach for the treatment of brainstem gliomas.

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Acknowledgements

This work was supported by the Pediatric Brain Tumor Foundation Institute Award to the University of California San Francisco, NIH Grants RO1NS093079, and by a generous gift from the Segal Family Foundation.

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Authors and Affiliations

  1. Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, 300 East Superior Street, Tarry 2-709, Chicago, IL, 60611, USA

    Nundia Louis, Xingyao He & Rintaro Hashizume

  2. Brain Tumor Research Center, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA

    Sharon Liu, Krystof Bankiewicz & Nalin Gupta

  3. Merrimack, Cambridge, MA, USA

    Daryl C. Drummond & Charles O. Noble

  4. Department of Pediatrics - Hematology, Oncology, Neuro-Oncology and Stem Cell Transplantation, Ann & Robert H Lurie Children’s Hospital of Chicago, Chicago, IL, USA

    Stewart Goldman

  5. Department of Neurology, University of California San Francisco, San Francisco, CA, USA

    Sabine Mueller

  6. Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA

    Nalin Gupta

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  1. Nundia Louis
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Correspondence to Rintaro Hashizume.

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Louis, N., Liu, S., He, X. et al. New therapeutic approaches for brainstem tumors: a comparison of delivery routes using nanoliposomal irinotecan in an animal model. J Neurooncol 136, 475–484 (2018). https://doi.org/10.1007/s11060-017-2681-8

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  • DOI: https://doi.org/10.1007/s11060-017-2681-8

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