Gliadel® Wafer Plus Temozolomide Show Promising Results in High Grade Malignant Glioma
May 18, 2005 - 9:57:38 AM
Guilford Pharmaceuticals Inc. today announced findings from a study of GLIADEL(R) Wafer (polifeprosan 20 with carmustine) and temozolomide used in combination to treat adult patients with newly diagnosed high grade malignant glioma. The data were presented at the 41st Annual Meeting of the American Society of Clinical Oncology in Orlando, FL.
Results of the ongoing, Phase II, multi-center, single-arm trial show acceptable toxicities when combining the two chemotherapeutic agents, and suggest that the combination may be given safely to patients with initial high grade malignant glioma.
During the trial, patients underwent surgical resection followed by implantation of GLIADEL(R), a localized chemotherapy inserted directly into the resection cavity. Patients were then treated with oral daily temozolomide and standard radiotherapy, followed by up to 18 cycles of oral monthly temozolomide.
"This is a logical follow-up to the work of Stupp et al. (New England Journal of Medicine, March 10, 2005 Volume 352, No.10)," said Renato V. LaRocca, M.D., FACP of Kentuckiana Cancer Institute PLLC and Principal Investigator of the study. "GLIADEL(R) and temozolomide are the only FDA- approved treatments clinically proven to prolong survival in patients with newly diagnosed high grade malignant glioma. We are encouraged by the initial results."
The sequential use of the these agents is based on the concept that treatment with GLIADEL(R) provides local chemotherapy at a time when the residual tumor cells would be otherwise untreated, prior to the commencement of radiation and systemic chemotherapy.
A major question has been the safety of combining the two treatment approaches, and these data begin to address the issue. Side effects in the study were similar to those reported in the medical literature and from previous Phase III trials for each treatment, along with surgical resection and radiation therapy.
About GLIADEL(R) Wafer
GLIADEL(R) Wafer is the only marketed cancer treatment capable of delivering chemotherapy directly to the site of a brain tumor, bypassing the blood-brain barrier and minimizing drug exposure to other areas of the body. GLIADEL(R) Wafer is a small, white to off-white dime-sized wafer comprised of a biodegradable polymer (polifeprosan 20) incorporating 7.7 mg. of carmustine (BCNU), a chemotherapeutic agent usually administered intravenously to treat a malignant glioma. Up to eight GLIADEL(R) Wafers can be implanted in the cavity created when a surgeon removes a brain tumor. There, they slowly dissolve, releasing BCNU directly to the tumor site in high concentrations, while minimizing drug exposure to other areas of the body.
Important Information About GLIADEL(R) Wafer
GLIADEL(R) Wafer is indicated in newly diagnosed patients with high-grade malignant glioma as an adjunct to surgery and radiation. GLIADEL(R) Wafer is also indicated in recurrent glioblastoma multiforme patients as an adjunct to surgery.
The following four categories of adverse events are possibly related to treatment with GLIADEL(R) Wafer during initial resection.
Frequencies are listed of events that occurred in a randomized trial of GLIADEL(R) Wafer and placebo, respectively: seizure (33.3% vs 37.5%); brain edema (22.5% and 19.2%); healing abnormalities (15.8% vs 11.7%); and intracranial infection (5.0% vs 6.0%). The following three categories of adverse events are possibly related to treatment with GLIADEL(R) Wafer for recurrent disease. Frequencies are listed of events that occurred in a randomized trial of GLIADEL(R) Wafer and placebo, respectively: post-operative seizure (19% vs 19%); healing abnormalities (14% vs 5%); intracranial hypertension (4% vs 6%) and intracranial infection (4% vs 1%).
Patients undergoing craniotomy for malignant glioma and implantation of GLIADEL(R) Wafer should be monitored closely for known complications of craniotomy, including seizures, intracranial infections, abnormal wound healing, and brain edema.
Cases of intracerebral mass effect unresponsive to corticosteroids have been described in patients treated with GLIADEL(R) Wafer, including one case leading to brain herniation. GLIADEL(R) Wafer contains carmustine and should not be given to patients who are allergic to carmustine. Carmustine can also cause fetal harm when administered to a pregnant woman.
The short and long-term toxicity profiles of GLIADEL(R) Wafer when given in conjunction with radiation or chemotherapy have not been fully explored.
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