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Gliadel
Wafer (polifeprosan 20 with carmustine implant) is indicated
in newly diagnosed patients with high-grade malignant glioma
as an adjunct to surgery and radiation. Gliadel is also
indicated in recurrent glioblastoma multiforme patients as
an adjunct to surgery. Gliadel provides localized delivery
of chemotherapy directly to the site of the tumor and is the
only FDA approved brain cancer treatment capable of doing
so.
Gliadel is a white, dime-sized wafer made up of a biocompatible polymer that contains the cancer chemotherapeutic drug, carmustine (BCNU). After a neurosurgeon removes a high-grade malignant glioma, up to eight wafers can be implanted in the cavity where the tumor resided. Once implanted, Gliadel slowly dissolves, releasing high concentrations of BCNU into the tumor site. The specificity of Gliadel minimizes drug exposure to other areas of the body. see review article here |
I
Interstitial chemotherapy for malignant gliomas: the Johns Hopkins
experience.
Department of Neurological Surgery, Johns Hopkins Medical Institutions, Baltimore, MD, USA. J Neurooncol. 2006 Dec 14;
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((R)) 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.
Gliadel wafer in initial surgery for malignant glioma: long-term follow-up of a multicenter controlled trial.
Department of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany. westphal@uke.uni-hamburg.de
OBJECTIVE: Adjuvant systemic chemotherapy increases survival of primary malignant glioma patients beyond 12-18 months. The only interstitial chemotherapy treatment approved for malignant glioma is Gliadel wafer containing carmustine (BCNU) placed in the resection cavity at surgery. Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial. Long-term follow-up of these patients was undertaken to determine the survival benefit at 2 and 3 years. METHODS: Survival proportions for the placebo and treatment groups over the 56-month study were estimated by the Kaplan-Meier method. Multiple-regression analyses using the Cox proportional hazards model included prognostic factors of age, KPS, and tumor type. A secondary analysis was conducted for 207 GBM patients. RESULTS: Of the 59 patients available for long-term follow-up, 11 were alive at 56 months: 9 had received BCNU wafers and 2 had received placebo wafers. Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years. Two of 207 GBM patients remained alive at the end of the follow-up period, both in the BCNU wafer-treated group. CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo.