Gliadel Implant

Generic Name: Carmustine
Product Name: Gliadel Implant

Indication

Carmustine is used in the palliative management, alone or in combination with other agents, of the following cancers:
– malignant glioma (type of brain tumour)
– multiple myeloma (often in combination with prednisone)
– HodgkinÂ¡Â¯s disease
– Non-HodgkinÂ¡Â¯s lymphoma
The implantable preparation of Carmustine, Gliadel Implant, is used to prolong life in patients with recurrent glioblastoma multiforme (a malignant brain tumour) who have had surgery.

Action

Carmustine is an alkylating agent. This is a type of antineoplastic agent that works by interfering with DNA in a number of ways. Extra molecules, called alkyl groups, are added to DNA, which causes it to break apart as the cell tries to replace them. Carmustine also interferes with the bonds between DNA strands, stopping them from separating, which is a step required in DNA replication. By replacing bases (important components of DNA) alkylating agents also create mismatching, another way to stop DNA being reproduced properly. All these changes occur when a cell is preparing to divide, and the permanent damage they cause results in cessation of division and cell death.
Gliadel Implant is a special way to deliver Carmustine directly into the surgical cavity created after brain tumour removal. Once placed in the cavity, Carmustine is released from the implant and exerts its antineoplastic effects. 70% of the implant is spontaneously and metabolically degraded after 3 weeks.

Dose advice

BiCNU injection
– 200mg/m2 intravenously every six weeks (in patients who have never had therapy with Carmustine before)
– dose should be adjusted accordingly when BiCNU is used in combination with other chemotherapeutic agents
– repeat dose should not be given before the 6 weeks is up
– total cumulative dose should not exceed 1500mg/m2
Preparation of intravenous solution
– dissolve powder in supplied 3ml of solvent
– add 27ml of water for injections
– solution should be administered via intravenous infusion over no less than one hour
– contact with skin causes burning and hyperpigmentation and should be avoided
– only glass containers should be used for preparation and administration
Gliadel Implant
After surgery to remove as much of the brain tumour as possible, the surgeon will implant up to 8 implants in the cavity left behind.

Common side effects

Bone marrow toxicity is very common, and results in decreased numbers of platelets, red blood cells and white blood cells. Anaemia and increased rates of bleeding and infection may occur.
Nausea and vomiting occur very commonly.
Changes in the lung occur commonly, and symptoms include breathing difficulties and a non-productive cough. These may occur up to years after cessation of therapy.
Convulsions are commonly seen with use of the Gliadel Implant, but most were mild and did not affect survival. Swelling of the brain is also reported regularly, as were infections of the brain.

Haematological – Carmustine will suppress the production of all blood cells hence the reason the drug is given in cycles.

Nausea / Vomiting – Moderate
Pulmonary Fibrosis – usually with cumualtive doses over 1.4g/m2. Thrombophlebitis – Pain at the injection site Nephrotoxicity and Hepatotoxicity.

Optic Nerve damage can occur.

Uncommon side effects

The following are seen with use of BiCNU injection:
– changes in liver function tests
– decrease in kidney size
– kidney failure
– facial flushing
– burning at the injection site
– low blood pressure
– increased heart rate
– chest pain
– headache
– allergic reaction
The Gliadel Implant may cause some additional effects:
– high or low blood pressure
– diarrhoea
– constipation
– trouble swallowing
– changes in blood sugar levels
– neurological effects including depression, insomnia, amnesia and paranoia
– pneumonia
– urinary incontinence