New study: Seizures and Tumor Progression in Glioma Patients with Uncontrollable Epilepsy Treated with Perampanel.
https://www.ncbi.nlm.nih.gov/pubmed/29970574 (abstract only)
http://sci-hub.tw/10.21873/anticanres.12737 (PDF download from sci-hub)
"Obvious seizure control was observed in 10 analyzed patients (100%) and 6 patients (60%) became seizure-free"
"Tumor volume and peritumoral edema within 6 months were volumetrically analyzed by MRI-FLAIR images, and the volume changes were evaluated. The tumor volume decreased in eight of 9 patients during 6 months by FLAIR image (Figure 2) and increased in one (Case 9) of 9 patients"
See also
Seizure response to perampanel in drug-resistant epilepsy with gliomas: early observations
https://www.ncbi.nlm.nih.gov/pubmed/28492978
Stephen, thanks for the interesting study! I saw him, but at first I did not attach any importance to him. Now I carefully studied all the materials.
ReplyDeleteOf the 10 patients remaining in the study, there were 2 patients with glioblastoma.
1 of the patients with glioblastoma also used TMZ and BEV. However, the researchers suggest that the reduction of the tumor caused precisely PERampanel:
"These results suggested that bevacizumab had minimal effect on the results in this study and that the underlying mechanism for the reduction of tumor volume in response to the PER might be an antitumor effect rather than a mere reduction of peritumoral edema...
...MRI images of glioma patients showed tumor growth inhibition and/or peritumoral brain edema reduction in correlation with the plasma concentrations of PER"
The 2 nd patient with glioblastoma did not observe a decrease in the tumor. He did not accept Bev and TMZ.
2009 https://www.ncbi.nlm.nih.gov/pubmed/19636006
"Talampanel with standard radiation and temozolomide in patients with newly diagnosed glioblastoma: a multicenter phase II trial.
The stimulating survival of the results in methylated and unmethylated patients, suggesting that blocking AMPA receptors may be a useful strategy in newly diagnosed glioblastoma. "
PERampanel has been developed as a novel non-competitive AMPA-receptor antagonist and approved as adjunctive therapy for seizure treatment. PER has excellent brain penetration, a long half-life and drug concentration profile compared with talampanel.
2015 https://www.ncbi.nlm.nih.gov/pubmed/26018396
"Malignant gliomas like glioblastoma multiforme (GBM) release glutamate which causes excitotoxic death to surrounding neurons, thereby vacating room for tumor expansion. We report the case of a patient with GBM treated with the AMPA receptor blocker Perampanel (PER)...
In a group of patients with IDH 1 wild type and non-methylated MGMT a median survival of 199 days after surgery (i. e. 6.5 months) was described."
However, this patient lived 18 months. In addition, he had only a biopsy.
If patients do not have epilepsy, can Perampanel be considered as an addition to the cocktail because of its effect on tumor growth or are there more effective similar drugs?
Seizure activity might be a predictor of tumor response to perampanel. If a patient never had seizures it could mean there is not an excess of glutamate in the area around the tumor. My guess is that patients never having seizures (in the absence of anti-epileptic drugs) would be less likely to have a tumor response to perampanel, but that is only a guess.
Delete