tients with recurrent malignant glioma, one at 64 days and the second at 92 days after implantation, were analyzed for content. The following table presents the results of analyses completed on these remnants.
COMPOSITION OF WAFER REMNANTS REMOVED FROM TWO PATIENTS ON RE-OPERATION
|
Component |
Patient A |
Patient B |
|
Days After GLIADEL® Wafer Implantation |
64 |
92 |
|
Anhydride Bonds |
None detected |
None detected |
|
Water Content (% of wafer remnant weight) |
95-97% |
74-86% |
|
Carmustine Content (% of initial) |
<0.0004% |
0.034% |
|
Carboxyphenoxypropane Content (% of initial) |
9% |
14% |
|
Sebacic Acid Content (% of initial) |
4% |
3% |
The wafer remnants consisted mostly of water and monomeric components with minimal detectable carmustine present.
CLINICAL STUDIES
Primary Surgery
A randomized, double-blind, placebo-controlled clinical trial was conducted in adult patients with newly-diagnosed high-grade malignant glioma undergoing initial craniotomy for tumor resection. This trial determined the safety and efficacy of GLIADEL® Wafer implants plus surgery and radiation therapy compared to placebo implants plus surgery and radiation therapy. Two hundred and forty patients with newly-diagnosed malignant glioma were enrolled. The most common tumor type was Glioblastoma Multiforme (GBM) (n=207), followed by anaplastic oligoastrocytoma (n=11), anaplastic oligodendroglioma (n=11), and anaplastic astrocytoma (n=2). GLIADEL® Wafers were implanted at the time of the surgery in 120 patients and placebo wafers were implanted in 120 patients. The majority of patients received 6-8 wafers. The majority of patients (93/120, 77.5% in the GLIADEL® Wafer group and 98/120, 81.7% in the placebo group) with newly-diagnosed malignant glioma received a standard course of radiotherapy (55 to 60 Gy) typically starting 3 weeks after surgery. There were 17 patients (14.2%) in the GLIADEL® Wafer group and 12 patients (10.0%) in the placebo group who received systemic chemotherapy during the study. All six patients with anaplastic oligodendroglioma received chemotherapy within 30 days of GLIADEL® Wafer implantation. Patients were followed for at least three years or until death. Only one patient was lost to follow-up. Median survival increased from 11.6 months with placebo to 13.8 months with GLIADEL® Wafer (p-value <0.05, log-rank test). The hazard ratio for GLIADEL® Wafer treatment was 0.73 (95% CI: 0.56-0.95).
Kaplan-Meier Overall Survival Curves for Patients Undergoing Initial Surgery for a High-Grade Malignant Glioma
When only patients with Glioblastoma multiforme were included in the analysis, the hazard ratio with GLIADEL® Wafer treatment was 0.78 (95% CI: 0.59-1.03, p=0.08, log-rank test).
Surgery for Recurrent Disease
A randomized, double-blind, placebo-controlled clinical trial was conducted in adult patients with recurrent malignant glioma. This trial determined the safety and efficacy of GLIADEL® Wafer implants plus surgery compared to placebo implants plus surgery.
Ninety-five percent of the patients treated with GLIADEL&
