What is Gliolan?
Gliolan is a powder for the preparation of a solution to be taken by mouth. It contains the active ingredient 5-aminolevulinic acid hydrochloride (30 mg / ml).
What is Gliolan used for?
Gliolan is used in adult patients with malignant glioma (a type of brain tumor). Gliolan allows a better visualization of the tumor during the removal operation. Given the small number of patients with malignant glioma, the disease is considered rare and on 13 November 2002 Gliolan was designated as an "orphan medicine" (a medicine used for rare diseases).
The medicine can only be obtained with a prescription.
How is Gliolan used?
Gliolan should only be used by experienced neurosurgeons, competent in malignant glioma surgery and with a deep knowledge of brain anatomy, who have followed a training course in fluorescence-guided surgery.
The recommended dose of Gliolan is 20 mg per kilogram of body weight to be taken two to four hours before anesthesia. The powder should be dissolved in 50 ml of normal water by the nurse or pharmacist before being administered to the patient. Gliolan should be used with caution in patients with liver or kidney problems.
How does Gliolan work?
The active substance in Gliolan, 5-aminolevulinic acid, is a sensitizing agent used in photodynamic therapy. It is absorbed by the cells of the body, where it is converted by enzymes into fluorescent chemicals, particularly protoporphyrin IX (PPIX). Because glioma cells absorb more of the active ingredient and convert it more quickly to PPIX, higher levels of PPIX accumulate in cancer cells than in healthy tissues. When illuminated by a blue light at a precise wavelength, the PPIX present in the tumor emits an intense red light, while the healthy brain tissue appears blue. This allows the surgeon to more clearly visualize the tumor during surgery and to remove it more accurately, saving healthy brain tissue.
What studies have been carried out on Gliolan?
The effects of Gliolan were first tested in experimental models before being studied in humans. However, since 5-aminolevulinic acid is a substance found in nature and is already used in other situations, the company also presented the data in the literature.
Gliolan was the subject of a main study conducted on 415 patients with malignant glioma about to undergo a neurosurgical operation for tumor removal. The outcome of the intervention was compared between patients treated with Gliolan (operated under blue light) and patients who were not given any medicine to improve the visibility of the tumor (operated under normal white light). The main efficacy parameter was the percentage of patients in which there was no visible tumor on the brain scan performed at 72 hours from the intervention as well as on the percentage of survival at six months without relapse or tumor expansion (disease progression). The brain images obtained by scanning were examined by an expert who did not know which patients had been treated with Gliolan.
What benefit has Gliolan shown during the studies?
Surgical removal of the brain tumor was more complete in the cases where Gliolan was used. At 72 hours after surgery, 63.6% of patients who received Gliolan showed no visible tumor on their brain scan, compared to 37.6% of patients not treated with Gliolan. At six months, 20.5% of patients receiving Gliolan were still alive with no disease progression compared to 11% of patients who had not taken Gliolan.
What is the risk associated with Gliolan?
The most common side effects seen with Gliolan are due to a combination of factors consisting of the medicine as well as anesthesia and tumor removal. The most frequently observed side effects (ie in more than 1 patient in 10) are anemia (low number of red blood cells), thrombocytopenia (low number of platelets), leukocytosis (high levels of leukocytes, a type of white blood cells) and an increase in blood enzyme levels in the blood (bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase and amylase). For the full list of all side effects reported with Gliolan, see the Package Leaflet.
Gliolan should not be used in patients who may be hypersensitive (allergic) to 5-aminolevulinic acid hydrochloride or porphyrins. It should also not be used in patients with porphyria (inability to break down porphyrins) and in pregnant patients.
Why has Gliolan been approved?
The Committee for Medicinal Products for Human Use (CHMP) noted that the goal of surgical treatment of malignant glioma is to remove the tumor as much as possible while saving healthy brain tissue, and concluded that Gliolan improves the ability to distinguish the tumor from healthy brain tissue during surgery, it increases the percentage of patients whose tumor is completely removed and prolongs the survival of patients without disease progression.
The committee decided that Gliolan's benefits outweigh its risks in visualizing malignant tissue during malignant glioma removal and therefore recommended that Gliolan be given marketing authorization.
What measures are being taken to ensure the safe use of Gliolan?
Before the medicine is marketed, the manufacturer of Gliolan will organize courses in all Member States to inform neurosurgeons on how to use the medicine safely and effectively during surgery.
Other information about Gliolan:
On 7 September 2007 the European Commission issued to the medac Gesellschaft für klinische
Spezialpräparate mbH a marketing authorization for Gliolan, valid throughout the European Union. For a summary of the opinion on Gliolan of the Committee for Orphan Medicinal Products click here.
The full EPAR for Gliolan can be found here.
Last update of this summary: 07-2007.
