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General disorders and administration site conditions
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common
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Peripheral oedema, neck pain, accidental injury, back pain, allergic reaction, asthenia, chest pain, sepsis
The following four categories of adverse events are possibly related to treatment with GLIADEL Implant.
Seizures:
In the initial surgery trial, the incidence of seizures within the first 5 days after implantation was 2.5% in the GLIADEL Implant group.
In the surgery for recurrent disease trial, the incidence of post-operative seizures was 19% in patients receiving GLIADEL Implant. 12/22 (54%) of patients treated with GLIADEL Implant experienced the first new or worsened seizure within the first five post-operative days. The median time to onset of the first new or worsened post-operative seizure was 3.5 days in patients treated with GLIADEL Implant.
Brain Oedema:
Development of brain oedema with mass effect (due to tumour recurrence, intracranial infection, or necrosis) may necessitate re-operation and, in some cases, removal of GLIADEL Implant or its remnants (see section 4.4).
Healing Abnormalities:
The following healing abnormalities have been reported in clinical trials of GLIADEL Implant: wound dehiscence, delayed wound healing, subdural, subgaleal or wound effusions, and cerebrospinal fluid leak.
In the initial surgery trial, cerebrospinal fluid leaks occurred in 5% of GLIADEL Implant recipients. During surgery, a water-tight dural closure should be obtained to minimise the risk of cerebrospinal fluid leak (see section 4.4)
Intracranial Infection:
In the initial surgery trial, the incidence of brain abscess or meningitis was 5% in patients treated with GLIADEL Implant.
In the recurrent setting, the incidence of brain abscess or meningitis was 4% in patients treated with GLIADEL Implant.
In a published clinical study, cyst formation after GLIADEL Implant treatment has been reported. This reaction occurred in 10% of the patients observed in the study, however, the formation of cysts is possible after resection of a malignant glioma.
4.9 Overdose
Not applicable.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antineoplastic agents, ATC Code: L01AD0I
Preclinical data
GLIADEL Implant delivers carmustine directly into the surgical cavity created after tumoural resection. On exposure to the aqueous environment of the cavity the anhydride bonds in the copolymer are hydrolysed, releasing carmustine, carboxyphenoxypropane and sebacic acid. The carmustine released from GLIADEL Implant diffuses into the surrounding brain tissue and produces an antineoplastic effect by alkylating DNA and RNA.
Carmustine is spontaneously both degraded and metabolised. The alkylating moiety thus produced and presumed to be chloroethyl carbonium ion, leads to the formation of irreversible DNA cross-links.
The tumourcidal activity of GLIA
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