Oligo Treatment

Hello everyone,

In a couple weeks I'll be beginning proton radiation therapy. I have a basic cocktail and diet strategy for the 6 week treatment and I wanted to run it by this blog community while also asking a few questions.

My story so far:

Focal seizure in Oct 2018.

4.5cm mass, frontal/parietal, no contrast enhancement, everything else typical for an oligo.

Surgery late Dec. GTR, no visible tumor remains.

Pathology: Grade III oligo, with 10/10 HPF mitosis, dense cellularity, moderate atypia, no vascular proliferation, no necro.

TMB 6.8
IDH1 mut
TERT mut
CIC mut
1p19q codel
P53 retained
ATRX retained
MGMT methylated

Current plan is proton+TMZ then up to 12 cycles of TMZ.

Did 1 cycle of TMZ in between surgery and radiation start.

Cocktail

Keppra, 1g x 2
Longvida, 1.6g x 2
GTE 1g (450mg egcg) x 2
PSK 1.5g x 2
Maitake, 50mg x 2
CBD  (don't have it yet, still considering dosage)
Omega-3 3g (total EPA+DHA)
Pterstilbene 150mg x2
Resveratrol 250mg x2
D3 5000 IU x2
Berberine, 600mg x3
Silymarin, 450mg x3
Probiotics via yogurt or pills (occasional, can reduce gut diversity?)
Selenium 200mcg
Melatonin, 10-20mg
Magnesium, ~200-300mg

Still trying to get
Celebrex
Chloroquine

Ketogenic diet rough plan
72h fast 3 days prior
Protein under 65g, carbs under 20g and GKI as close to 1 as possible.
1000cal per day, possible 20:4 intermittent fasts 3 days per week, alternating

Lots of walking and probably very light but consistent exercise throughout.

Questions

1) Will any of these supplements (antioxidants specifically) potentially interfere with oxidative stress on the tumor cells?

2)The majority of this cocktail and diet plan is ripped from GBM research and GBM/AA3 posts on here. Are there IDHmt/oligo specific supplements/drugs etc that I may be missing?

3) I've heard GTE can be toxic. I have Nusapure GTE and Swanson's Teavigo caps as well. What are people on here buying for EGCG?

4) Is chloroquine as promising to an oligo as it is to a GBM?

5) Is cal restriction necessary if I were regularly fasting, and vice versa? This is a bit of a grey area that I don't quite have figured out yet.

Also, as of now, I intend to save PC chemo for future recurrences. TMZ is a much less damaging chemo. My main concern with TMZ, however, is hypermutation. I'm not sure how to possibly mitigate that.

Thanks in advance.

Improvement of the ketogenic diet

In many studies, it has been shown that a ketogenic diet can be a useful supplement in the treatment of glioblastoma. I would like to discuss the improvement of this diet on the basis of recent research.

1. Ketogenic diet + α-lipoic acid and hydroxycitrate
2017 https://www.ncbi.nlm.nih.gov/pubmed/28122260
"To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models."

2016 http://crescopublications.org/pdf/CROOA/CROOA-2-019.pdf
"Combination of Metabolic Treatment of Aggressive Primary Brain Tumour
and Multiple Metastases of the Brain"
"We report the cases of 12 patients with advanced brain tumor. They were all treated with
conventional treatment and a combination of sodium R lipoate (800 mgbid), hydroxycitrate at 500 mg tid and low-dose naltrexone at 5 mg at bedtime. Eight patients had primary brain tumour (n=8 including five glioblastomas) four patients had multiple brain metastases."

2. Ketogenic diet + Fenofibrate ?
2016 https://www.ncbi.nlm.nih.gov/pubmed/26869992
"Our results reveal a new, intriguing aspect of cancer cell biology and highlight the benefits of fenofibrate as a supplement to both canonical and dietary (ketogenic) therapeutic approaches against glioblastoma."
2015 https://www.ncbi.nlm.nih.gov/pubmed/26172294
"Given that fenofibrate is a widely used non-toxic drug, we suggest its use in patients with glioblastoma multiforme (GBM)."
2017 https://www.ncbi.nlm.nih.gov/pubmed/28459367
"...the lipid-lowering agent fenofibrate...have potential to lower synthesis or effects of G(M)-CSF and thus deprive a glioblastoma of some of the growth promoting contributions of bone marrow and G(M)-CSF.
It's strange, but in this blog I did not find any information about Fenofibrate. So is it necessary to add it to the ketogenic diet?

3. Ketogenic diet + Inhibition of glutamine metabolism ?
2017 https://www.ncbi.nlm.nih.gov/pubmed/28720668
"Inhibition of glutamine metabolism slows the in vitro and in vivo growth of GLNHigh GBM cultures despite metabolic adaptation to nutrient availability, in particular by increasing pyruvate shuttling into mitochondria."
"...the pleiotropic metabolic inhibitor EGCG, targeting glutamine metabolism, specifically reduces tumor proliferation, in vitro and in vivo, of mesenchymal GLNHigh cells."
How can the findings of this study be used? Only EGCG can not inhibit glutamine metabolism. Maybe there are more options?

4. Ketogenic diet + Specialized medium-chain triglycerides (MCT) ?
2016 http://clincancerres.aacrjournals.org/content/22/10/2482
"MCTs were specifically chosen based on carbon chain lengths (C8:C10::97%:3%), which allow them to rapidly diffuse from the gastrointestinal tract into the hepatic portal system and travel directly to the liver where they are converted into ketone bodies."

5. What other ideas can you offer to enhance the effect of a ketogenic diet?

Wife's Cocktail

Hello, everyone.

My 36 YO wife was diagnosed with a GBM on 11/12/2015, just four days after giving birth to our first child, debulked of 60-80% on 12/15/2015 and had the Gold Standard from 1/5/2016-1/25/2016. We have been on a ketogenic diet since 1/8/2016. She is MGMT methylated

This is what my wife was/is taking so I wanted to know everyone's thoughts if they had any:

During Radiation/Chemo

• Zofran - 4mg/3X/day
• Dexa - 4mg/2X/day
• Temodar - 110mg/1X/day
• Valcyte - 450mg/4X/daily
• Keppra - 1000mg/2X day
• Celebrex - 200mg/1X/day
• Depakote - 250mg/3X/day
• Nexium - 20mg/2X/day
• Cannibis - 10-50mg/day as needed
• Mushroom extract (Matake) - 600mg/day
• Fish Oil - 1100 mg of EPA plus 120 mg of DHA (2X/day) (2 capsules)
• Super Bio Curcumin/Turmeric - 400mg/2X/day
• Multivitamin

After 1/25/2016 to today

• Dexa - 4mg/morning - 2mg/night
• Valcyte - 450mg/2X/daily
• Keppra - 1000mg/2X day
• Celebrex - 200mg/1X/day (finishing 1/19/2016)
• Depakote - 250mg/3X/day
• Nexium - 20mg/2X/day  (finishing 1/19/2016)
• Cannibis - 100-250mg/day as needed
• Mushroom extract (Matake) - 750mg/day
• Fish Oil - 2200 mg of EPA plus 240 mg of DHA (2X/day) (4 capsules)
• Super Bio Curcumin/Turmeric - 400mg/3X/day
• Brocolli sprout extract - 1000mg/2X/day (concerned about antioxidating effects)
• Green Tea - 1-2 cup/day
• ECGC - 400mg/1X/day (concerned about antioxidating effects)
• Pomegrante Extract  - 500mg/1X/Day (concerned about antioxidating effects)
• Vitamin D - 2000 IU/1X/day- potentially more (1 capsule)
• Multivitamin

Questions

She is getting pill fatigue so I'm wondering what I can do to reduce/add pills for the most impact:

1. Should we increase the antioxidants (ECGC, Pomegranate, VitaminD, and Broccoli Sprout Extract)?
2. We have DCA - is there a risk if we do that in addition to the ketogenic diet?
3. We anticipate having access to chloroquine in 20 days, is it too late to add that?
4. As a followup to the last question, the reason why we didn't add the chloroquine is that it's contra-indicated for Celebrex, which we felt was more important.
5. What is considered a "low-dose" of Celebrex?
6. Any other suggestions?

Green Tea Extract-EGCG-Liver Toxicity

I pay an annual fee to belong to Consumer Lab where some products are tests.  I just received this email that I thought I'd share:
"A large, government-funded study recently found that pills of green tea extract can be safe for many people, but some may experience adverse reactions, including elevated liver enzymes."

"Several U.S. government agencies sponsored a study of the safety of green tea extract given to over 1,000 postmenopausal women at risk for breast cancer. Twice a day for a year, women in the study took 2 capsules with both morning and evening meals, providing a total of 1,315 mg of catechins, of which 843 mg was EGCG(equivalent to about 4 cups of green tea), or a placebo. There was no statistically significant difference in the overall incidence of adverse events between the two groups, but women in the extract group were more likely to experience nausea and skin rashes/allergies and less likely to report diarrhea. In addition, 6.7% of the extract group, but only 0.7% of placebo group, experienced elevations in liver enzymes — a sign of liver injury – and these elevations tended to be greater in the extract group. Enzyme levels returned to normal with discontinuation of the extract in all but one person. The researchers noted that "Though green tea has typically been associated with antioxidant effects, recent evidence has demonstrated a strong pro-oxidant effect of green tea catechins (especially EGCG) that can cause hepatotoxicity when administered in high doses." (Dostal, Food Chem Tox 2015.

The American College of Gastroenterology's clinical guideline for diagnosing and treating drug-induced liver injury, published in 2014, lists green tea extract as one of the most common dietary supplements linked to liver injury and stresses the importance of patients experiencing symptoms of liver dysfunction to inform their doctors of any supplements they may be taking (see the LiverTox Database to search for medications and supplements that may cause liver injury). One of the authors of the guidelines noted that levels of catechins can be over 700 mg in some green tea extract pills and, "This can be particularly dangerous when the pills are taken multiple times a day."

In light of potential liver toxicity, a USP expert committee voted in June 2007 to require the following cautionary statement to appear on the labels for green tea extracts: Caution: Must take with a meal. In rare cases extracts from green tea have been reported to adversely affect the liver. Discontinue use and consult a healthcare practitioner if you have a liver disorder or develop symptoms of liver trouble, such as abdominal pain, dark urine, or jaundice. However, approval of the label requirement was deferred and, in April 2009, the USP announced that the proposed requirement was cancelled. According to a USP spokesperson contacted by ConsumerLab.com, monitoring of adverse event databases from June 2007 through February 2009 showed no additional reports of liver toxicity, but the USP continues to monitor the safety of green tea. However, it may be wise to follow the original proposed guidance to take green tea extract with a meal, as this was given some support from tests on dogs which found that high doses of green tea extract induced lethal toxicity when given without food, but showed no significant toxicity when given with food (Wu, Int J Toxicology 2011.

Green tea contains a small amount of vitamin K, which directly counteracts Coumadin's blood-thinning action; however, enormous quantities of green tea would be necessary to provide a significant amount of vitamin K."

Cocktail Profile for Jeremy (Mikes son)

Here is my sons cocktail.  Chloroquine is being taken one month on, one month off.  Disulfiram is being taken on TMZ days.  EGCG taken only when taking TMZ.  DCA taken continuously.  Artemisinin and its analogs taken on a rotation schedule, but schedule is modified as necessary so they will be taken concurrent with TMZ.

Tumor specifics:  IDH1 mutant.  P53 mutant.

Last MRI was July 26th.  Inoperable brain stem GBM continues to be absent and the resected GBM (100%) in the left hemisphere shows no recurrence.  More diffuse lower grade non enhancing tumor is stable since late last year.  Concurrent use of Optune.

	Morning		Evening
Artemisinin  100 mg  Caps   5 days on 5 off	2
Artesunate 50 mg caps   5 days on 5 off	3
Artemether   40  mg caps  5 days on 5 off			2
Fish oil with High EPA/DHA	2		2
DCA  ~17 mg/kg/day  wt is 82 kg	700 mg		700 mg
Longvida Curcumin	6		6
Lycopene 10 mg	1
Melatonin 20 mg			1
Super Coriolus	3		3
Maitake D Fraction	3		3
Berberine  500 mg / capsule	2		2
Vitamin D 10,000 IU capsules	2
Ultra Soy Extract	1
Selenium  200 mcg	1
Milk Thistle   300 mg/capsule	2		2
Thiamin  250 mg			1
Pterostilbene	3		2
Benfotiamine	1
EGCG    (take on days with temodar)			4
Zinc	50 mg
PRESCRIPTION MEDS
Temodar
Vimpat
Tagamet  (200 mg tablets)	2		2
Metformin  (1000 mg tablets)	1		1
Celebrex      200 mg tablets	2		1
Sertraline (Zoloft)   50 mg	1
Minocycline  (100 mg tablets)	1		1
Chloroquine Phosphate    250 mg tablets)	1
Disurfiram (takes days you are on Temodar)