Advanced interstitial chemotherapy for treating malignant glioma

ABSTRACT

Introduction: Glioblastoma multiforme (GBM) is the most prevalent primary neoplasm of the brain. Moreover, the prognosis of patients with GBM has been poor, with almost uniform progressive neurological impairment and rapid death. Despite the availability of multimodal treatments through surgery, focal radiation, and chemotherapy, no major progress has been reported until recently.

Area covered: The development of interstitial biodegradable carmustine wafers (Gliadel) for treating selected patients with malignant gliomas has resulted in marginal survival benefits in such patients (only approximately 2 months longer than that of those who did not receive the treatment). Therefore, this study summarizes several recent representative studies, presents emerging studies, and highlights the directions for additional developments in this area. An overview of the current knowledge of preclinical developments, efficacy and safety observed in clinical trials and practice following drug approval, and future avenues of research is imperative.

Expert opinion: Studies are being conducted to improve the efficacy of interstitial chemotherapy by using nanobiotechnology and polymeric material science in addition to different chemotherapeutic, antiangiogenesic, and gene therapy agents and growth factors. Nanocarrier-based noninvasive techniques may have considerable potential to enhance the efficacy of GBM treatment.

KEYWORDS:

• Blood–brain barrier
• carmustine wafers (Gliadel)
• interstitial chemotherapy
• local delivery
• malignant gliomas
• nanobiotechnology

Article highlight box

• Carmustine (Gliadel) wafers are the only interstitial chemotherapeutic agents approved for the treatment of malignant glioma; however, their therapeutic effect requires improvement to yield greater survival benefits.

• Conventional methods for enhancing drug concentrations in the brain, such as BBB disruption, intraventricular drug injection, and local therapy, are highly invasive and have potential risks of damaging the brain parenchyma, thus rendering them unsuitable for long-term treatment regimens.

• Nanobiotechnology plays a major role in enhancing the therapeutic efficacy of local delivery systems, namely CED and controlled-release polymeric systems.

• Compared with other materials, polymeric NPs are more stable and simpler to prepare and scale-up, in addition to being promising as a system for controlled drug release.

• New studies are being conducted for improving the treatment efficacy of GBM by combining different chemotherapeutic agents and numerous agents with therapeutic potentials for GBM such as gene therapy, antiangiogenic agents, and chemotherapeutic agents as well as cytotoxins.

• Nanocarriers may provide new avenues for brain cancer therapy.

This box summarizes key points contained in the article.

Declaration of interest

The authors thank Taipei Medical University (Contract No. TMU102-AE1-B08) and Chang Gung Memorial Hospital (Contract No. CMRPD3D0141) for financially supporting this study. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing assistance was utilized in the production of this manuscript provided by Wallace Academic Editing and funded by Taipei Medical University (Contract No. TMU102-AE1-B08).

Additional information

Funding

This work was supported by the Chang Gung Memorial Hospital [CMRPD3D0141]; Taipei Medical University [TMU102-AE1-B08].