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Over the last few weeks (and months) there have been a large number of discussions within the neurosurgery, oncology and pharmacy departments regarding the risks of using Gliadel® wafers in clinical practice.
For those of you who do not know, Gliadel wafers are carmustine-containing, “biocompatible polymer” lattice, fingernail-sized tablets that dissolve and degrade in contact with moisture. They are used specifically for high-grade malignant glioma excisions, where up to eight wafers are placed in the tumour bed after excision of the tumour. Carmustine is known variously around the world as carmustine, carchlormethine, carclormetine, BCNU and 1,3-bis (2-chloroethyl)-1-nitrosurea.
Patients with highly malignant gliomas have a poor prognosis. Even with aggressive treatment, few will survive beyond one year from diagnosis. Traditional treatments include external beam radiation, surgical resection and systemic chemotherapy. Isolated and combination treatments have been tried but none have borne out their efficacy in double-blind randomised controlled trials in primary malignant glioma. Carmustine has been used systemically to treat gliomas as it readily crosses the blood-brain-barrier, but owing to its relatively short half-life (around 20 minutes), it does not reach the target of action in concentrations as high as would ideally be the case.
After neurosurgical resection, the tumour invariably recurs within 2cm of the original tumour site due to the infiltrative nature of the tumour. This problem prompted investigations into novel treatments which led to the development of the BCNU wafer. One large study showed that the median survival of surgically resected patients whose tumour bed was treated with BNCU wafer increased by more than two months, to a median of 13.9 months.1
Other than the fact that this is a remarkable treatment – and that the concept is so simple that I wonder why nobody produced this medicine years ago – there are a few other intriguing factors for pharmacy which have not been reported to the same extent and require a bit of thought from you pharmacists out there.
Our principal concern came from the fact that neurosurgeons, theatre staff and neurosurgical nurses would be treating and caring for patients treated with chemotherapy but without any formal training in the use and disposal of cytotoxic agents. The theatre nurses and ADOs had no idea about the disposal of contaminated packaging and instruments. One of the main complications of Gliadel wafers is the higher risk of CSF leak. Post resection, the placebo-treated patients had only a 0.8% chance of developing a CSF leak, whereas the BNCU-wafer patients had a risk of 5%. A CSF leak in a BNCU-treated patient could be considered a cytotoxic spillage, but none of our nurses were trained to deal with this. We had two main choices in dealing with this:
• Have our solid-tumour oncology wards look after these patients, with the risk that the patient develops neurological complications that the nurses are not trained for.
• Write a lot of protocols and policies, develop training packages and education programmes for the theatre and ward staff so that they know about correct disposal of cytotoxic waste and can manage spillages effectively.
The second option won out. This is a major use of stretched resources and requires a lot of commitment from a lot of staff.
Have you considered how you might deal with this in your area? Or have you already devised a solution? I’m keen to hear your views! Post your ideas on this and I hope we can give a few other centres a heads-up on dealing with the problem, before a serious problem occurs.
Until next time . . .
1. Westphal M, Hilt DC, Bortey E et al. A phase III trial of local chemotherapy with biodegradable carmustine (BCNU) wafers (Gliadel wafers) in patients with primary malignant glioma. Neuro-Oncology 2003;5:79-88. Available online at: http://neuro-oncology.dukejournals.org/cgi/reprint/5/2/79.pdf