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Updated: Jun 8, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
A comprehensive outlook on intracerebral therapy of malignant gliomas
Carlo Buonerba1, Giuseppe Di Lorenzo, Alfredo Marinelli
1Cattedra di Oncologia Medica, Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Università degli Studi Federico II, Naples, Italy.
Abstract:
Glioblastoma multiforme (GBM) is the most frequent and aggressive malignant glioma (MG), with a median survival time of 12-15 months, despite current best treatment based on surgery, radiotherapy and systemic chemotherapy. Many potentially active therapeutic agents are not effective by systemic administration, because they are unable to cross the blood-brain barrier (BBB). As intracerebral administration bypasses the BBB, it increases the number of drugs that can be successfully delivered to the brain, with the possibility of minor systemic toxicity and better effectiveness. This review summarizes the results of the extensive clinical research conducted on intracerebral therapy. Biodegradable drug carriers, implantable subcutaneous reservoirs and convection-enhanced delivery (CED) represent the main techniques for intracerebral delivery, while conventional chemotherapy agents, radiolabeled antibodies and receptor-targeted toxins are the main classes of drugs for intracerebral therapy. At the present time, biodegradable carmustine wafers, commercialized as Gliadel(®), are the only FDA-approved treatment for intracerebral chemotherapy of MG, but intracavitary delivery of mitoxantrone and radiolabeled antitenascin antibodies via implantable reservoirs has yielded promising results in uncontrolled trials. The pressure-driven flow generated by CED can potentially distribute convected drugs over large volumes of the brain, independently on their intrinsic diffusivity. Nevertheless, prominent technical problems, like backflow, are yet to be properly addressed and contributed to the disappointing results of two phase III trials that investigated CED of cintredekin besudotox and TransMid™ in patients with recurrent GBM.
Insights
Intracerebral therapy bypasses the blood-brain barrier to deliver glioblastoma drugs directly to the brain. While biodegradable wafers are FDA-approved, other methods show promise but face technical challenges.
Area of Science:
- Neuro-oncology
- Drug Delivery Systems
- Clinical Trials
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain cancer with poor prognosis despite standard treatments.
- Systemic drug delivery is limited by the blood-brain barrier (BBB), hindering effective treatment.
- Intracerebral administration offers a way to bypass the BBB, potentially improving drug efficacy and reducing systemic toxicity.
Purpose of the Study:
- To review clinical research on intracerebral therapy for malignant gliomas (MG).
- To summarize the main techniques and drug classes used in intracerebral delivery.
- To evaluate the current status and challenges of intracerebral treatment strategies for GBM.
Main Methods:
- Review of clinical research on intracerebral drug delivery methods.
- Analysis of biodegradable drug carriers, implantable reservoirs, and convection-enhanced delivery (CED).
- Examination of drug classes including chemotherapy agents, radiolabeled antibodies, and toxins.
Main Results:
- Biodegradable carmustine wafers (Gliadel®) are the only FDA-approved intracerebral chemotherapy for MG.
- Intracavitary delivery of mitoxantrone and radiolabeled antitenascin antibodies shows promise in uncontrolled trials.
- Convection-enhanced delivery (CED) faces technical challenges like backflow, impacting trial outcomes for recurrent GBM.
Conclusions:
- Intracerebral delivery strategies offer potential advantages over systemic administration for brain tumors like GBM.
- Further technical advancements are needed to overcome challenges in methods like CED for widespread clinical application.
- Ongoing research into intracerebral therapies is crucial for improving outcomes in malignant glioma patients.
