My dad aged 59 had a grand mal seizure 25th Feb 2019; operation/debulking 7th March 2019, Radiochemotherapy 30 sessions in May 2019. Completed 2nd round of 5/23 chemo cycle. He is negative for IDH, MGMT.
Overall he has been doing ok with the treatment. The only set back was when he had around 3 to 4 multiple grand mal seizures around 30th June 2019. We had no warning about that seizure and our medical team didn't warn us that he could get seizures from the radiation swelling 4 weeks post radiation (we thought maybe just during radiation treatment). He had no side effects during radiation treatment period itself - we were shocked that it happened -
Question 1: Seizures post radiation 4 weeks after radiation
I guess it is a "normal" side effect? We thought seizures would be a side effect later on when the treatment might stop working. The hospital put him into an induce coma for 2 days to stop the seizures. He took steroids for about 6 weeks after and has come off the steroids now and has had no further seizures. We are also surprised that nobody ever mentioned to us to have buccal midazolam injection at hand as when we called the ambulance, the paramedics had to call the fire brigade for an advance paramedic to inject IV anti seizure drug. If we had the buccal midazolam this might have prevented the multiple seizures. He now carries the buccal midazolam injections around.
Question 2: Foot twitching post seizure, same side as tumor
His Keppra was 2 x 500mg up until then and now they have increased it to 2.5g per day and added Phenytoin. Since that seizure he has had a foot twitch during the night and a sore pain in his thumb - can be normal effects from the swelling and tumor? The tumor is on the left side and the twitch is on the left side which is unusual? The doctors would expect the tumor to effect the right side.
We stopped doing the cocktail after 30th June with the big seizure then but then continued with Chloroquine and Celebrex a week later. We have since started back doing the cocktail (see below).
Question 3: Celebrex
I read the Brain Tumor Charity do not support taking Celebrex and some articles says it is not good to take, what is the opinion about it now given the new clinical trail data? Also it seems like it can react with Epainutin (Phenytoin) so we give it to him in the evening. - https://www.thebraintumourcharity.org/brain-tumour-diagnosis-treatment/treating-brain-tumours/treatments-licensed-other-illnesses/celecoxib-celebrex/
Question 4: Daily timetable of cocktail
Do people have a daily timetable to avoid interactions between anti-seizure drugs and others?
Question 5: Disulfiram
We have disulfiram but we have never given it to him as it seems to interact with the Epanutin (Phenytoin). Have people taken this together?
Question 6: Curcumin
He is taking Doctors Best High absorption Curcumin with C3 Complex and Bioperin 1000 mg. This tablet he finds hard to digest because it is very big and solid even using a tablet cutter. Is there a different brand which people recommend which is easier to take?
Question 7: Reishi
He is taking Reishi as part of a multi-mushroom supplement for Brain function called Fungi Perfecti, MycoBotanicals for the Brain. However we read on Sloan Kettering that reishi is not good to take?
Question 8: Ranitidine in absence Cimetidine
He is taking Ranitidine as we could not get cimetidine. We asked a friend in Spain to get the cimetidine but they got us cinitaprida normon? It is for treating stomach ulcers but I guess its totally different as it doesn't appear to be a H2 antihistamine. We were not sure if it was any use giving it to my dad? We have not given him the Cinitaprida normon but we give him 75mg Ranitidine a day.
Question 9: Mebendazole
He is taking Mebendazole 100mg daily - i know its well below the dosages a human would need to take compared to the mouse study? Do people take much higher doses? The studies do not seem clear about it but I know it is used in Care Oncology alot?
Question 10: Antibiotics Doxycycline/Minocycline
Antibiotics – he was only on these when during radiochemo phase but not now…Care oncology seems to recommend doxycycline and a rotation with other antibiotics such as minocycline? Should he start taking this too? How much do people take, do people rotate each month? Surely antibiotics will cancel out the effects of building up the immune system?
Question 11: Valacyclovir and other antiviral drugs?
Should we look into taking Valacyclovir? (I know there is no right or wrong cocktail). If so, how do people get this, how long do they take it for? We read somewhere that people can get tested for different virus's in their system such as Herpes? Is there a test for CMV? Is there any other herpes/CMV drugs we should take?
Question 12: Amino acid Brain supplements L-tyrosine and N-acetyl cysteine
We had been giving him L-tyrosine and N-acetyl cysteine and we stopped after the seizure. I know Cheryl Broyle mentioned using NAC. I don't know if these 2 compounds have good/bad effects on the brain? For a normal brain they are meant to be good.
Question 13: Vitamin C IV
I read up on Vitamin C IV and I don't know if we should try that - it doesn't seem clear if it is effective or not and it doesn't mention it could flush out the anti-seizure drugs?? Those studies mention N-acetyl cysteine reverses the benefits of IV Vit C??
Question 14: Berberine
Only recently ive seen many people taking berberine. Are many people taking this supplement?
Question 15: Other Repurpose drugs
Interesting article with a few extra repurpose drugs which I have not mentioned above. Not too familar with them and the cocktail?
Prescribed by GB:
Keppra - Anti seizure. he was on 500 mg x 2 day but since the seizure it is now 2.5g per day.
Keppra - Anti seizure. he was on 500 mg x 2 day but since the seizure it is now 2.5g per day.
Epanutin - Phenytoin. Anti seizure..100 mg x 3
Atorvastatin – Cholesterol treatment 20 mg per day
Metformin – diabetic, 500 mg twice a day
Ramipril - To lower blood pressure, 5mg
Atorvastatin – Cholesterol treatment 20 mg per day
Metformin – diabetic, 500 mg twice a day
Ramipril - To lower blood pressure, 5mg
Melatonin 20 mg
Off-label prescription/non prescription drugs:
- Chloroquine Phosphate, 250 mg/day
- Celebrex (Celecoxib), 200 mg/day
- Mebendazole 100mg - this is the recommended daily dose for normal pinworm treatment but i read people are on more?
- We could not get Tagamet (cimetidine), so we were using Ranitidine, another Histamine H2 receptor (usually used for stomach uclers - repurpose of Cimetidine is immune, anti invasion. We do not know if Ranitidine is a good replacement but apparently cimetidine can interact with Celebrex, but I think Ranitidine has reduce side effects to Tagamet). - we have not restarted Ranitidine yet
Supplements: Majority of these we get from iherb apart from the coriolus versicolor which we order from evitamins.
- Coriolus versicolor extract PSK/PSP (Turkey tail mushroom)
- Maitake-D mushroom extract, 1200mg per day
- Reishi mushroom extract - for immune. We got Fungi Perfecti mycobotanicals for the Brain
- Curcumin High absorption extract 1000mg
- Omega-3-6-9 1200 mg
- Boswellia extract 500 mg – to reduce edema
- Standard multivitamin/multimineral capsules, time-release
- Probiotic (Garden of Life, Dr. Formulated Mood+ 16 strains)
- Vitamin D, 5,000 IU/day
- Selenium (we just used a multi purpose vitamin)
- Soy Extract (we were using Soya Isoflavonoids which I think contains genistein which is meant to be good).
- Resveratrol 200mg
- Green Tea Extract ECGg 400 mg
Supplements: Majority of these we get from iherb apart from the coriolus versicolor which we order from evitamins.
- Coriolus versicolor extract PSK/PSP (Turkey tail mushroom)
- Maitake-D mushroom extract, 1200mg per day
- Reishi mushroom extract - for immune. We got Fungi Perfecti mycobotanicals for the Brain
- Curcumin High absorption extract 1000mg
- Omega-3-6-9 1200 mg
- Boswellia extract 500 mg – to reduce edema
- Standard multivitamin/multimineral capsules, time-release
- Probiotic (Garden of Life, Dr. Formulated Mood+ 16 strains)
- Vitamin D, 5,000 IU/day
- Selenium (we just used a multi purpose vitamin)
- Soy Extract (we were using Soya Isoflavonoids which I think contains genistein which is meant to be good).
- Resveratrol 200mg
- Green Tea Extract ECGg 400 mg
- Silymarin
Stopped taking - should we take again?
- NAC N-acetyl cysteine– I noticed Cheryl Broyle was taking this but it is not on Stephen’s cocktail list.
- L-Tyrosine 500mg – I did not see this on any cocktail list but it is an amino acid which is meant to help with brain function.
- L-Tyrosine 500mg – I did not see this on any cocktail list but it is an amino acid which is meant to help with brain function.
Never started this but should we after the seizure? Can it interfere?:
- Disulfiram and he has not started this.
Celecoxib (Celebrex) is a COX-2 inhibitor. COX-2 is the rate-limiting enzyme in the production of prostaglandin E2 (PGE2). There is some evidence COX-2 inhibitors could be useful in various combinations, for example during immunotherapy (PGE2 can have immunosuppressive effects), or during radiation (PGE2 can be produced by tumors as a response to radiation treatment). I've summarized some of the preclinical evidence on this page
ReplyDeletehttp://astrocytomaoptions.com/radiation/
under "Radiation and COX-2 inhibitors"
I wouldn't be surprised if adding Celebrex alone to standard therapy doesn't change median survival significantly, but the cocktail approach aims at synergies in multi-drug combinations. See the discussion of the "Nile Distributary Problem" in the CUSP9* publication by Richard Kast et el.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226667/
Drugs.com has an interactions checker that I have found to be useful.
https://www.drugs.com/drug_interactions.html
Lots of people here take the Longvida formulation of curcumin, which has been discussed extensively on the blog.
Yep, cinitapride is used for the same diseases as cimetidine, but the mechanism of action is very different and is not an H2 antagonist like cimetidine etc. There is some positive preclinical evidence for ranitidine for use in cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006904/
In clinical trials for high grade glioma, they started at doses of 500 mg three times daily (1500 mg per day).
https://clinicaltrials.gov/ct2/show/NCT01729260
I've seen recommendations by these trial investigators for daily mebendazole doses of 100 mg/kg daily, or more (6000 mg daily for a 60 kg adult).
In the CUSP-ND cocktail protocol (which hasn't been tested in humans) we proposed a dose of 50 mg/kg in three divided doses (or 3000 mg daily for a 60 kg adult).
Mebendazole has poor bioavailability, which might explain why the drug is pretty well tolerated even at high doses. I don't understand the rationale for Care Oncology using such low doses of mebendazole to treat cancer. Small doses might be enough to kill parasites in the intestine, but to treat tumors enough drug has to first get into the bloodstream, and then for brain tumors it further has to cross the blood-brain barrier. I'm not sure 100 mg would provide anything more than a placebo effect in the case of brain tumors. The trials of high dose mebendazole for high grade glioma haven't been published, so its not clear even high doses are enough to help with brain tumors.
There is more evidence on the use of minocycline for brain tumors compared to doxycycline. Remember Care Oncology protocol was developed as a general cancer therapy, not really specific to any type of cancer, while brain tumors have unique challanges to do with drugs being able to cross the blood-brain barrier. There have actually been clinical trials with minocycline for recurrent GBM, although I don't think the results have been spectacular.
https://sno.confex.com/sno/2017/meetingapp.cgi/Paper/4856
Some of the publications on Valcyte for GBM have generated a lot of controversy. See my review of this here:
http://astrocytomaoptions.com/repurposed-drugs/
There are clinical trials underway testing iv vitamin C for GBM, at the University of Iowa and University of Nebraska. The trials at University of Nebraska were terminated, but there is still one ongoing at U of Iowa. https://clinicaltrials.gov/ct2/show/NCT02344355
Hopefully we'll soon have more data on this on the basis of these trials.
First-in-human phase 1 clinical trial of pharmacological ascorbate combined with radiation and temozolomide for newly diagnosed glioblastoma
ReplyDeletehttps://www.ncbi.nlm.nih.gov/pubmed/31427282
Hi Stephen, thanks so much for replying to my post. It means so much to us that you take time out to provide information and take the time to reply to us.
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