The FDA in 2003 approved implanting biodegradable discs infused with Carmustine inside the patient's skull at the time of surgery as a treatment for GBM brain cancer (#10). The big advantage of this approach is that the drug gets released over time directly into the tumor site, and does not need to cross the blood-brain barrier. The brand name for this type of medication/delivery system is Gliadel®.
The wafers are about dime-size in diameter and usually 7-8 wafers are placed in the cavity created by the surgical removal of the tumor. The wafers release most of their Carmustine within a few days (#11).
In one study, at 12 months after surgery, 63% of the Gliadel patients were still alive, and 19% of those in the placebo group were still alive. Some concern was expressed about the validity of these findings - read the whole report for more information about this (#11).
Side effects of this treatment can include nausea, vomiting and constipation. Anti-nausea drugs can be prescribed to ameliorate some of the side-effects (#12).
There have been instances of cerebral edema showing up later on in patients who have received the Gliadel® treatment (#13). This swelling of the brain can increase pressure inside the skull.
There have also been some instances of Adverse Events occurring in patients who have been treated with Gliadel®, and then have later had to be operated on again, for recurrent tumors (#14). In addition to cerebral edema there have been cases of cysts being discovered when additional surgeries have become necessary.
A Canadian study reported Adverse Events including convulsions, confusion, brain edema and aphasia. But similar levels of Adverse Events were reported in at least one of the trials studied, for both the Gliadel® and placebo groups (#15). The study concluded that there was a "significant survival benefit for Gliadel® as compared with placebo."
Another study (#17) shows that adding Gliadel and Avastin to the standard Temozolomide for newly diagnosed GBM added 9 months to average survival time and doubled progression-free survival.
A study (#18) suggests that Gliadel may attract CD8+ Killer T Cells to the area of the tumor. This report is quite new (February 2018), and we need to be on the lookout for other combinations of Gliadel with immunotherapies.
Finally, An important study (#16) performed a meta-analysis of a large number of Gliadel clinical trials. Among the important points raised in this report are:
A) Widespread use of Gliadel has been somewhat limited because its use may preclude enrollment in subsequent clinical trials.
B) Overall survival rates at 1, 2, and 3 years were greater for patients receiving Gliadel treatments, over the placebo groups.
C) And much improved results were noted when Temozolomide was administered in combination with Gliadel.
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Sources for this article include:
1. How Gliadel Wafer Is Used
http://gliadel.com/patient/how-gliadel-is-used.php
2. Gliadel Wafer and Floruescence-Guided Surgery With 5-ALA Followed by Radiation Therapy And Temozolomide in Treating Patients With Primary Glioblastoma
https://clinicaltrials.gov/ct2/show/NCT01310868
3. Gliadel Wafer (polifeprosan 20 with carmustine implant)
4. Gliadel Wafer
https://www.webmd.com/drugs/2/drug-20903/gliadel-wafer-implant/details
5. Carmustine and Gliadel
https://dtp.cancer.gov/timeline/flash/success_stories/S1_carmustine.htm
6. Safety and efficacy of carmustine (BCCNU) wafers for metastatic brain tumors
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4866053/
7. The role of Gliadel wafers in the treatment of newly diagnosed GBM: a meta-analysis
8. Gliadel Wafer and Flourescence-Guided Surgery With 5-ALA Followed by Radiation Therapy and Temozolomide in Treating Patients With Primary Glioblastoma
https://clinicaltrials.gov/ct2/show/NCT01310868
9. Overview of Gliadel®
https://virtualtrials.com/gliadel/
10. FDA Approves Gliadel Wafer for Treatment of Malignant Gliomas
http://www.patientadvocate.org/news.php?p=235
11.Panel Recommends FDA Approval of Gliadel for GBM
http://www.cancernetwork.com/articles/panel-recommends-fda-approval-gliadel-gbm
12. Gliadel Side Effects Center
https://www.rxlist.com/gliadel-side-effects-drug-center.htm
13. Cerebral edema associated with Gliadel wafers: Two case studies
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1871626/
14. Risk Factors for Adverse Events after Implantation of BCNU Wafers in High-grade Gliomas
https://www.ncbi.nlm.nih.gov/pubmed/26136324
15. Gliadel wafers in the treatment of malignant glioma: a systematic review
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2002480/
16. Survival outcomes and safety of carmustine wafers in the treatment of high-grade gliomas: a meta-analysis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4368843/
17. Advantages and disadvantages of combined chemotherapy with carmustine wafer and bevacizumab in patients with newly diagnosed glioblastoma
https://virtualtrials.com/newsarticle.cfm?item=6453
18. Tumor microenvironment after biodegradable BCNU wafer implantation: special consideration of immune system.
https://virtualtrials.com/newsarticle.cfm?item=6452
George Bigham
Bigham.George@gmail.com
March 25th, 2018
This page was created on 03/21/2018 and last updated on 04/21/2019