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Which Drug or Drug Delivery Method Can Change Clinical Practice for Brain Tumor Therapy?

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  • First Online:
Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

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Abstract

Despite advances in anticancer drug discovery and development, there has been little improvement in the prognosis and outcome of malignant brain tumors. Often and repeatedly it has been found that promising experimental agents for brain tumors have had little impact on the disease in clinical trials. These disappointing results can be partially explained by the inability to deliver therapeutic agents to the CNS across the physiological barriers (the blood–brain, blood–tumor, and blood–CSF barriers). The impediment posed by these barriers leads to failure of the delivered drug to reach the desired target in adequate concentrations. This chapter shortly reviews the leading strategies that try to improve drug delivery to brain tumors in view of their likelihood to change clinical practice. Strategies that use systemic delivery and those that utilize local delivery are critically reviewed. In addition challenges posed for drug delivery by the combined treatment with anti-angiogenic therapy are outlined. For future development all new drugs or delivery systems must adhere to basic clinical expectations. These include besides an anti-tumor effect, a verified favorable toxicity profile, an easy introduction into clinical practice, feasibility of repeated or continuous administration and compatibility of the drug or strategy for any tumor size and brain location. Adherence to these essentials will enable a change in clinical practice

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Abbreviations

Abbreviation AUC:

Area under the curve

BBB:

Blood–brain barrier

CED:

Convection-enhanced delivery

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

ECF:

Extracellular fluid

EGF:

Epidermal growth factor

HD-CTx:

High-dose chemotherapy

MTX:

Methotrexate

P-gp:

P-glycoprotein

PEG:

Polyethylene glycol

RES:

Reticuloendothelial system

SAE:

Severe adverse effects

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Gaffin Center for Neuro-Oncology, Hadassah Hebrew University Medical Center, Ein Kerem, 12000, Jerusalem, 91120, Israel

    Tali Siegal M.D.

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  1. Tali Siegal M.D.
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Correspondence to Tali Siegal M.D. .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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© 2014 American Association of Pharmaceutical Scientists

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Siegal, T. (2014). Which Drug or Drug Delivery Method Can Change Clinical Practice for Brain Tumor Therapy?. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_24

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