- Department of Neurosurgery, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
- Iowa Brain and Spine Institute, Waterloo, IA, USA
- Dvision of Neurosurgery, Department of Surgery, University of Chicago, Chicago, IL, USA
Correspondence Address:
Patrik Gabikian
Dvision of Neurosurgery, Department of Surgery, University of Chicago, Chicago, IL, USA
DOI:10.4103/2152-7806.111305
Copyright: © 2013 Abel TJ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.How to cite this article: Abel TJ, Ryken T, Lesniak MS, Gabikian P. Gliadel for brain metastasis. Surg Neurol Int 02-May-2013;4:
How to cite this URL: Abel TJ, Ryken T, Lesniak MS, Gabikian P. Gliadel for brain metastasis. Surg Neurol Int 02-May-2013;4:. Available from: http://sni.wpengine.com/surgicalint_articles/gliadel-for-brain-metastasis/
Abstract
With therapies for systemic malignancy improving, life expectancy for cancer patients is becoming increasingly dependent on control of brain metastatic disease. Despite improvements in surgical and radiotherapy modalities for control of brain metastasis, the prognosis for patients with brain metastases is poor. The development of controlled release polymers has lead to novel new therapies for malignant brain tumors consisting of direct surgical delivery of chemotherapy agents to the tumor bed and sustained chemotherapy release over a prolonged period of time. Although there is a large body of literature in support of BCNU polymer wafer for primary brain malignancy and experimental brain metastases, clinical studies evaluating the BCNU polymer wafer for brain metastatic disease are relatively sparse. In this review, we discuss the role of the BCNU polymer wafer for brain metastasis focusing specifically on rationale for use of locally delivered sustained release polymers, history of the BCNU polymer wafer, and emerging studies examining the role of the BCNU polymer wafer for metastatic brain tumors.
Keywords: Brain tumor, brain metastasis, BCNU polymer wafer, gliadel chemotherapy, local delivery
INTRODUCTION
The development of controlled release polymers has lead to novel new therapies for malignant brain tumors consisting of direct surgical delivery of chemotherapy agents to the tumor bed and sustained chemotherapy release over a prolonged period of time. The BCNU polymer wafer has been used clinically for several years and was Food and Drug Administration (FDA)-approved for use in patients with malignant glioma in 1996.[
RATIONALE FOR USE OF BIS-CHLOROETHYLNITROSOUREA POLYMER WAFERS FOR BRAIN METASTASES
Clinical rationale
Cerebral metastasis is a common result of systemic malignancy and a primary cause of morbidity and mortality for cancer patients.[
Despite significant advances in cancer therapies leading to improved systemic control, a large number of patients with cerebral metastatic disease die from intracranial progression in the setting of good systemic control.[
With the incidence of cerebral metastatic disease increasing and control of systemic malignancy improving despite often-uncontrolled intracranial spread, optimizing management of metastatic brain tumors is a great priority. The current mainstay of therapy consists of some combination of surgical resection, whole brain radiation therapy, and stereotactic radiosurgery.[
Mechanistic rationale
Tumors respond to chemotherapy as a result of sensitivity of tumor cells to administered chemotherapy and the ability to deliver therapeutic concentrations of the chemotherapeutic agent to the tumor.[
The overall chemosensitivity of metastatic brain tumors is a function of both inherent chemosensitivity and acquired chemoresistance. Inherent chemosensitivity is determined primarily by tumor histology, which determines the cytologic structure and function of the tumor and ultimately determines cell response. For example, small cell lung cancer (SCLC) is considered one of the most chemosensitive histologies, whereas melanoma is considered minimally chemosensitive.[
Because of these limitations to standard systemically administered chemotherapeutics, there has been a clinical need to explore novel alternatives, such as the BCNU polymer wafer. Surgically delivered local chemotherapeutics such as the BCNU polymer wafer bypass the BBB completely, which allows for therapeutic concentrations of chemotherapeutic to be delivered directly to the tumor bed and surrounding tissues. Locally delivered polymer chemotherapy agents do not directly address the issue of tumor sensitivity and chemoresistance, but if more chemotherapies are developed for surgical delivery via a sustained release polymer, it could enhance the repertoire and effectiveness of chemotherapy options for CNS metastases that normally do not cross the BBB.
History of the BCNU polymer wafer
Development
In 1976, Langer and Folkman developed a polymer specialized for the sustained release of macromolecules using ethylene vinyl acetate (EVAc).[
In 1993, Tamargo et al. reported the first use of BCNU-embedded polymer wafers in a rat model of 9L gliosarcoma.[
The BCNU polymer wafer and primary brain malignancy
To date, numerous clinical trials have been performed to evaluate the safety and efficacy of the BCNU polymer wafer for treatment of glioma both alone and in combination with other therapies.[
The BCNU polymer wafer and brain metastases
Despite the promising results of BCNU polymer wafers in treatment of malignant glioma and the obvious mechanistic advantages of local administration of chemotherapy for metastatic brain tumors, studies evaluating the use of the BCNU polymer wafer against metastatic brain tumors are limited both in experimental animal research and human clinical trials.
Animal studies
In 1996, Ewend et al. published the first experimental use of the BCNU polymer wafer with external beam radiotherapy in various animal models of metastatic brain tumor.[
Human clinical trials
In 2007, Ewend et al. reported their experience on the BCNU polymer wafer for treatment of solitary brain metastasis in conjunction with radiation therapy.[
Other preliminary studies of the BCNU polymer wafer for brain metastases have been presented as abstracts at various meetings.[
CONCLUSION
Despite ample evidence demonstrating safety and efficacy of the BCNU polymer wafer for malignant glioma, research evaluating its use for metastatic brain tumor is relatively limited. Preliminary studies in both animal models and humans suggest that use of the BCNU polymer wafer is safe and may decrease local recurrence in metastatic brain tumors. Although in animal models there is a reported survival benefit with BCNU polymer wafer treatment,[
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