Interstitial chemotherapy for malignant gliomas: the Johns Hopkins experience
Malignant gliomas are very difficult neoplasms for clinicians to treat. The reason for this is multifaceted. Many treatments that are effective for systemic cancer are unable to cross the blood-brain barrier and/or have unacceptable systemic toxicities. Consequently, in recent years an effort has been placed on trying to develop innovative local treatments that bypass the blood-brain barrier and allow for direct treatment in the central nervous system (CNS)—interstitial treatment. In this paper, we present our extensive experience in using interstitial chemotherapy as a strategy to treat malignant brain tumors at a single institution (The Johns Hopkins Hospital). We provide a comprehensive summary of our preclinical work on interstitial chemotherapy at the Hunterian Neurosurgery Laboratory, reviewing data on rat, rabbit, and monkey studies. Additionally, we present our clinical experience with randomized placebo-controlled studies for the treatment of malignant gliomas. We compare survival statistics for those patients who received placebo versus Gliadel® as initial therapy (11.6 months vs. 13.9 months, respectively) and at the time of tumor recurrence (23 weeks vs. and 31 weeks, respectively). We also discuss the positive impact of local therapy in avoiding the toxicities associated with systemic treatments. Furthermore, we provide an overview of newer chemotherapeutic agents and other strategies used in interstitial treatment. Finally, we offer insight into some of the lessons we have learned from our unique perspective.
KeywordsCarmustine·Gliadel® Glioblastoma multiforme Interstitial chemotherapy Malignant glioma
Disclosure: Dr. Henry Brem and the Johns Hopkins University are entitled to a share of royalty by MGI Pharma, Inc. on potential sales of some products that are in development and described in this work. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. Dr. Prakash Sampath is a member of the Speakers Bureau for MGI Pharma, Inc., formerly Guildford Pharmaceuticals, Inc.
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