Abstract
Development of effective treatments for high-grade glioma (HGG) is hampered by (1) the blood–brain barrier (BBB), (2) an infiltrative growth pattern, (3) rapid development of therapeutic resistance, and, in many cases, (4) dose-limiting toxicity due to systemic exposure. Convection-enhanced delivery (CED) has the potential to significantly limit systemic toxicity and increase therapeutic index by directly delivering homogenous drug concentrations to the site of disease. In this review, we present clinical experiences and preclinical developments of CED in the setting of high-grade gliomas.
Highlights
Glioblastoma (GBM) is the commonest malignant brain tumor of primary origin
A subsequent trial investigated the co-infusion of topotecan with gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA), which enabled direct visualization of infusate. This trail was unique in its use of the Cleveland Multiport Catheter (CMC), which was designed for convection-enhanced delivery (CED) [27]
Delta-24-RGD is a conditionally replication-competent adenovirus that was investigated in a phase I study in 13 patients with recurrent glioblastoma
Summary
Despite an annual incidence of less than 10 per 100,000 people worldwide, this aggressive and invasive glioma has a devastating prognosis with a current 1-year survival rate of. 42.8% and 5-year survival rate at an abysmal 7.2% [1]. Often characterized as molecularly heterogenous tumors, the recent c-IMPACT- consensus classified GBM as isocitrate dehydrogenase (IDH)-wild type WHO grade IV glioma with microvascular proliferation, necrotic lesions, or possessing > 1 of the following genetic alterations: TERT promoter mutation, EGFR gene amplification, +7/−10 chromosome copy number changes [2,3]. Complete resection of malignant tissue is limited by the highly invasive nature of this malignancy, thereby creating a reliance to chemotherapeutic options such as temozolomide, which have traditionally been delivered systemically. The restrictive blood–brain barrier (BBB) and toxicities from systemic delivery have limited therapeutic options
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