Cocktail questions, also foot twitching?

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/

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.12785

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?

https://www.mskcc.org/cancer-care/integrative-medicine/herbs/reishi-mushroom

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?

https://www.canceractive.com/article/repurposing-old-off-patent-drugs-as-new-and-effective-cancer-treatments

https://www.frontiersin.org/articles/10.3389/fphar.2019.00681/full

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. 

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

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

- 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.

Never started this but should we after the seizure? Can it interfere?:

- Disulfiram and he has not started this. 

High-dose intravenous vitamin C at home

I want to try to do a drop of high-dosage vitamin C at home.

In some studies, such solutions were used:
- Ascorbic acid MEGA-C-PLUS®, 500 mg / mL (25g / 50mL) from Merit Pharmaceuticals
(in the Riordan Clinic https://riordanclinic.org/research-study/vitamin-c-research-ivc-protocol)
- Ascorbic acid, 500 mg / mL (25g / 50mL) from Mylan Institutional, LLC NDC # 67457-118-50
- Ascorbic acid, 500 mg / mL (25g / 50mL) from McGuff Pharmaceuticals, Inc. Item # 008232
(in this study https://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30062-4)
- Ascorbic acid, 500 mg / mL (25g / 50mL) from Bioniche Pharma (Rosemont IL)
(in this study https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260161/)

Maybe someone knows some kind of pharmacy or clinic in the US where I can buy (with a prescription) this ascorbic acid 500mg/ml?

1. In the protocol of the Riordan Clinic (https://riordanclinic.org/research-study/vitamin-c-research-ivc-protocol/) details how to dilute Ascorbic acid, 500 mg / mL.

2. This study also details how to prepare a solution of ascorbic acid 500 mg / ml:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260161/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260161/bin/pone.0029794.s001.pdf

3. Description of infusion in this study:

http://journals.sagepub.com/doi/10.1177/1534735415622010

"For the first 2 IVC doses, the initial infusion rate was 0.5 g/min, starting at 15 g of vitamin C with an appropriate amount of carrier fluid (sterile water and ringer’s lactate, depending on the concentration of ascorbic acid infused). For the next 2 doses, 25 g of vitamin C was given at 0.5 g/min, with an appropriate amount of carrier fluid, with addition of 200 mg of magnesium chloride to prevent vascular spasm. For the subsequent 2 doses, 50 g of vitamin C was given at 0.5 g/min with an appropriate amount of carrier fluid and 200 mg of magnesium chloride. After the first 6 doses, 75 g of vitamin C was given at 0.5 g/min with an appropriate amount of carrier fluid and 200 mg of magnesium chloride. Vitamin C dosage was then increased to 100 g with 400 mg of magnesium chloride for patients with extremely aggressive tumors."

4. Description of infusion in this study:

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0120228

https://doi.org/10.1371/journal.pone.0120228.s002

"Vitamin C infusates were prepared using ascorbic acid 500 mg/mL for injection USP (supplied as single-use 50 mL glass ampules) as a gift from Alveda Pharma Canada, Ltd. The stock solution was diluted in sterile water to achieve an osmolarity of approximately 900 mOsm/L. Any air bubbles formed during preparation were promptly evacuated. The solutions were delivered to the clinical research unit covered by an opaque bag, allowed to come to ambient temperature, and infused by calibrated infusion pump within one hour of preparation. Water and other drinks (preferably sugar-free) were provided and the patients encouraged to consume them freely before, during and after IVC infusions. The dose of vitamin C was 1.5 g/kg body weight when the body mass index (BMI) was 30 kg/m2 or less, and normalized to the body weight corresponding to BMI 24 kg/m2 for patients with a BMI > 30. The vitamin was infused at a constant rate over a period of 90 minutes for doses up to 90 g, and over a period 120 minutes for doses > 90 g."

"When the dose is less than 15 g the stock solution is diluted with lactated Ringer’s to guarantee sufficiently high osmolality to permit intravenous administration. When the dose is equal to or greater than 15 g, the infusate is brought to the required concentration using sterile water to achieve an osmolality between 500 and 900 mOsm/L. The osmolality maybe calculated from the molecular weight of AA assuming it is completely dissociated in aqueous solution. Examples are given as follows.

15 g (30 mL stock qs 300 mL using sterile water): 570 mOsm/L.

30 g (60 mL stock qs 500 mL using water): 684 mOsm/L.

60 g (120 mL stock qs 900 mL using water): 760 mOsml/L.

70 g (140 mL stock qs 1100 mL using water): 725 mOsml/L.

80 g (160 mL stock qs 1100 mL using water): 829 mOsml/L.

90 g (180 mL stock qs 110 mL using water): 933 mOsml/L.

100 g (200 mL stock qs 1200 mL using water): 950 mOsml/L.

110 g (220 mL stock qs 1400 mL using water): 896 mOsml/L.

120 g (240 mL stock qs 1400 mL using water): 977 mOsml/L.

130 g (260 mL stock qs 1600 mL using water): 926 mOsml/L.

140 g (280 mL stock qs 1800 mL using water): 887 mOsml/L.

 Intravenous infusions are administered via a peripheral or central intravenous catheter at a rate of 0.5 g/minute to approximately 1 g/minute, and not usually faster than approximately 1 g/minute. At the dose of 1.5 g/kg an infusion will typically last 105 minutes."

5. https://pdfs.semanticscholar.org/864a/c9c15a0d529702662135020d5b1323dab276.pdf?_ga=2.149448115.464894850.1525286351-1963972769.1523462509
"In this study, we used MEGA-C-ACID PLUS® (500 mg/ml, Merit Pharmaceuticals, Los Angeles, California). This source of AA was used because other clinical preparations in Japan contained preservatives, and there was no data regarding the safety of these substances when administrated at high doses.
AA was given through a central vein catheter on days 7, 9, 11, 14, 16, and 18 during the 2nd course of the CHASER regimen (Fig. 1). A small test dose of 15 g AA in 250 ml Ringer＇s lactate solution was administered at a rate of 0.5 g/min on day 7, and then 75 g of AA dissolved in 1,000 ml of distilled water was administered at a rate of 1 g/min on each of the other days listed above.
In order to prevent hypocalcemia due to the chelating effect of AA, 0.5 g magnesium sulfate was added to every 500 ml of AA solution."

6. https://link.springer.com/article/10.1007%2Fs00280-013-2179-9
Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer.

"The solution to be infused contained the appropriate amount of ascorbic acid in sterile water for injection with calcium chloride, magnesium chloride, and potassium chloride.
Incipient changes during the study: the concentrations of calcium and magnesium in the infusion solution were reduced to the same concentrations that appear in blood (5 and 2 mEq/L, respectively). In addition, potassium was lowered to 16.7 mEq/L, which delivers 10 mEq/h, an infusion rate that is considered safe for all patients. Ascorbic acid remained at 100 g/L and was infused at 1 g/min."
_____________________

In the American clinic Riordan, as seen from the attached table, 75 grams of ascorbic acid is diluted with 750cc of sterile water (probably this is water for injections). But why is the final volume 750cc? Can anyone help to understand the string from the table, for example about 75 grams?

* cc = cubic centimeter

Sensitization of cancer (stem) cells by Doxycycline to Vitamin C, Berberine, Chloroquine and others

Dear all,


I recently came across the below study, which I thought was rather interesting:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620172/

The authors used incrementally higher dosages of Doxycycline (12.5 uM, 25 u.M, 50 uM) in vitro on cancer cells in an effort to create metabolically inflexible cells and to test whether these would be then be more sensitive to metabolic inhibitors, including natural agents (Vitamin C and Berberine) and various meds (Atovaquone, Irinotecan, Sorafenib, Niclosamide, Chloroquine, and Stiripentol).

The cancer cells in the study ended up being highly sensitized to some of these agents, for example Vitamin C (4-10 x more sensitive), Berberine and Chloroquine. It's noteworthy that, following Docycycline treatment, cells became sensitive to Vitamin C at a dosage level which is reachable orally (IC-50 = within the range of 100uM - 250 uM). My understanding is that newer Vitamin C formulations using oral Liposomal delivery (e.g.: https://www.livonlabs.com/cgi-bin/start.cgi/liposome-encapsulated/lypo-spheric-vitamin-c.html) can reach concentrations of up to 400 uM in the blood, a level at which cell elimination in vitro was in excess of 90%).

I'm curious if these results could be replicated at least directionally in a human setting, as it would be a rather cost effective and non-toxic approach. Any thoughts?

A few questions I'd have for example are:

1. Is this Doxycycline cell sensitization replicable in a human setting? If so, at what dosage?
2. Is there any chance an oral Vitamin C formulation (e.g. Liposomal) could replicate the effect seen in vitro? Alternatively, I presume IV infusions would do the job?
3. Which of the other agents would be the most feasible otherwise?

Best regards,
John

Vitamin c

There is very little here about vitamin c. Our naturopath recommends high dose vitamin c. What are your thoughts?

CUSP9 without being in a trial

I have asked my daughters NO to prescribe the drugs used in the CUSP9 'Concept of Treatment Trial', he has agreed to try to get them prescribed  minus the Auranofin.

He has agreed this as they can't offer anything else. Her recurrence is diffuse in cerebellum, extends to the brain stem and shows small area of enhancement round original site of left temporal lobe.
 He said Gamma knife not an option, no trials available and she is not fit to fly for magnetic or any other therapy due to lack of mobility, tiredness etc.

At present I am trying to get health insurance co to pay for Avastin, which they are saying isn't licenced in UK.

My concern is,  that apart from twice weekly blood tests I am going to have to try to oversee her treatment with these drugs and I'm very nervous. But there doesn't seem to be an alternative.

NO has said to stop Valproic Acid, presumably because of interaction.

Any thoughts gratefully received.

I.V. for Vitamin C to boost Chemo and overall Immune strength?

Stephen -
I got a strong recommendation from a leading brain cancer oncologist (he appeared on Ben Williams' documentary) to take I.V. for Vitamin C with observational evidence of it significantly helping the patients. I am working on getting prescription next. I am finding lot of materials on web as well about Vitamin C against cancer, though FDA has not approved it. Any insights on this? thanks!