Thursday, 26 September 2019

Repurposing perampanel (glutamate receptor blocker)?

About a week ago there was a major study published in the journal Nature called "Glutamatergic synaptic input to glioma cells drives brain tumour progression".

I've uploaded the full study to the Pathology folder in the Brain Tumor Library.

The study discovers a communication network between neurons and glioma cells, with certain effects (including tumor invasiveness) mediated by AMPA type glutamate receptors. Furthermore, these effects were blocked in vitro by the approved AMPA glutamate receptor antagonists, perampanel.

Perampanel was approved in 2012 for  partial seizures and generalized tonic-clonic seizures for people older than 12 years, so could also have anti-seizure effects in addition to potential anti-tumor effects.

The relevant discussion from the Nature paper is as follows:
The selective non-competitive AMPAR antagonist perampanel is an approved antiepileptic drug shown to have potential antitumour effects in patients with glioma and warrants further investigation. Chronic administration of perampanel to xenografted mice decreased the proliferation of GB cells as determined by in vivo imaging of tumour regions over time (Fig. 5j, k, Extended Data Fig. 9a) independently of cell-autonomous effects as determined by an in vitro proliferation assay (Extended Data Fig. 9b).

This is not the first paper to discuss perampanel effects on glioma and/or seizure control for glioma patients. For example:

AMPA receptor antagonist perampanel affects glioblastoma cell growth and glutamate release in vitro

Adjunctive perampanel for glioma-associated epilepsy.

Feasibility of modified Atkins diet during radiation - retrospective study

Feasibility of a modified Atkins diet in glioma patients during radiation and its effect on radiation sensitization.

Monday, 23 September 2019

Avastin alone?

Further to a recent previous post.

3 months of TMZ 5/23 showed that chemo is not working for unmethylated GBM. The tumor is very active according to MRI comparison between July and September 2019. There was alot of swelling which is currently being reduced with 16 mg steroids per day in the past week. Speech has improved alot with this. Was told it is too close to previous radiation or surgery to have either done again.

2 weeks ago clonazepam was prescribed 10mg x 2 and Keppra increased to 1500mg x 2 and Phenytoin 300mg in the morning -  all of this is keeping seizures, twitches and focal seizures away.

Oncologist is going to start IV Avastin today and stop all treatment - asked if it was pallatiative but answer no it is not pallatiative treatment yet. Thought it was unusual to go ahead with Avastin by itself and not combine it with another chemo treatment such as lomustine?

Have been following cocktail since during radiation treatment back in April 2019 which I posted about in previous post. This includes daily chloroquine (155mg active ingredient); celebrex 200mg; metformin 500mg x 2; Atorvastatin; ramipril; ranitidine 75 mg; mebendazole; melatonin 20mg.

Also the usual daily supplements of mulitvitamin; 16 strain Probiotics; PSK; Maitake D; ; Mushroom supplement mix for brain (lions mane 300mg; bacopa 250 mg; reishi 150 mg; gotu kola 130 mg; ginko 120 mg); curcumin (longvida); vitamin D; ECG; Milk Thistle; Berberine; Boswellia; Resveratrol; Omega 3-6-9; Soy Falvonoids (geinistein)

Wondering if anyone has any experience of just Avastin being prescribed? I am wondering what is even the point in doing avastin alone? Appears to have more side effects and very little extra benefits, or OS? I was optimistic that Richard Geiber had Avastin and low dose TMZ but that doesnt seem to be on offer to us? Or any chemo alternative?

Very disappointing TMZ stupps protocol + cocktail did not seem to work. 

Friday, 6 September 2019

CUSP9v3. Gliovac. Toca 511

Dear Stephen, dear all!
1) What do you think about GLIOVAC(
And about DCVax?
What is the difference between them?
And there is also dendritic cell vaccine in IOZK (the cheapest one).
Which one has better statistics? Is it worse trying?
2) What about CUSP9v3 protocol effectiveness? Want to try it for my mom. A lot of discussions here in the blog, but can't find information about latest clinical trials results.
3) What do you think about Toca 511? Any experience?
Thank you!

Cocktail question, Fluoxetine or Celebrex?

Dear Stephen and all,

I have a question concerning my girlfriend's father. He is 57 years old. He was diagnosed with a Grade IV, MGMT unmethylated Glioblastoma in the left occipital lobe, September 2018. After the surgery, he received radiotherapy and chemotherapy using VAL-083 in China during 08/11/2018 - 27/06/2019. He had an MRI scan on 20/08/2019 and there is a 17mm*10mm GBM recurrence in the left temporal lobe.

Now his oncologist suggests receiving the standard 5/23 Temozolomide treatment. Since his GBM is MGMT unmethylated, we want to have the cocktail to enhance the performance of Temozolomide for him. He is taking Metformin, Verapamil, Chloroquine and Keppra. We want to choose 1 more medicine from Fluoxetine and Celebrex, which one is better?

Thank you for your help! Best wishes to everyone.

Details of the condition of my father are listed below:

  • On 28/09/2018 he had surgery due to a tumor in the left occipital lobe. According to the biopsy, he was diagnosed with a Grade IV Glioblastoma Multiforme, MGMT unmethylated, ki67 70%, IDH1/2(-), 1p/19q non-codeleted, non-diffuse.
  • On 08/11/2018, he began to receive radiotherapy and chemotherapy using VAL-083 with a dose of 30mg/m2 IV. But soon he suffered severe myelosuppression and both radiotherapy and chemotherapy are stopped for 2 weeks. After that, the dose of VAL-083 was tuned to 20mg/m2.
  • On 24/06/2019, the assessment via MRI is CR I class, complete response (that shows the VAL-083 is effective for him)
  • On 27/06/2019, he finished the clinical trial, including 10 cycles of treatment using VAL-083.
  • On 20/08/2019, MRI shows that there is a 17mm*10mm enhanced mass in the left temporal lobe (the original tumor was in left occipital lobe).