Quite urgently seeking Suggestions

Hi Everyone,

I have been a long-time reader of this amazing blog that Stephen created and regularly check it for any posts about new treatments or therapies. I am really happy to see that Stephen still occasionally posts new studies and answers some questions. 

I am quite urgently seeking advice on next steps in relation to treatment for my partner (of 18 years), who is a very physically active person and despite everything that has occurred, remains very positive. She is 40 years old.

Background:

We are based in Australia and she was diagnosed in December 2011 (2 days before Christmas!) with a low grade Astrocytoma in the left Temporal Lobe. 

2012 (February): She underwent craniotomy that resulted in a subtotal resection – it was an awake craniotomy owing to the tumour’s location near important speech areas.

Histopathology of the sample was unfortunately not very detailed and only confirmed a Low Grade Astrocytoma with a very low KI67 of < 1%

2015 (February): The lesion increased in size over the years (pretty much doubled) to 55 x 34 x 49mm – so a second surgery was performed that again resulted in subtotal resection.

Histopathology results showed – Low Grade Astrocytoma, IDH1 Mutated.

A retrospective FoundationOne profile was obtained on this sample in 2017 and only showed 2 mutations: IDH1 (R132H) mutated and TP53 (R175H).

2017 (September): The tumour continued to grow and extended into the frontotemporal region and insula. Another Surgery was conducted in two sessions due to expected length, and a large portion of tumour from the temporal and frontotemporal regions was removed, as well as a small portion from the insula.

Histopathology results showed – IDH1, 1p/19q co-deletion, ATRX lost, TP53 Mutated, KI67 of 2%

A Caris profile was also obtained which also showed that the tumour was not MGMT methylated – although after asking Stephen about this at the time, he said that MGMT was a bit of a hit and miss due to the heterogeneity found in tumours – so we remained hopeful that MGMT may still be methylated in most of the tumour given it is typical of low grade gliomas.

 

* The Caris report conflicted with the histopathology and showed ATRX intact.

2018 (January): Managed to get Bayer to sponsor my partner to take part in their IDH1 Inhibitor trial (BAY1436032), went to L.A and got knocked down at the last minute due to not completely satisfying their RANO requirements!

(September) Sought out the top neurooncologist + radio oncologist team in Sydney and she started IMRT then moved on to a round of TMZ which finished in early 2019.

2019 : MRI’s showed decent shrinkage in the tumour volume for the first 6 months then stable.

2020 (January) : MRI showed slight enhancement in the original temporal lobe resection cavity + strangely an enhancing nodule on the right ventricle. These were determined by the neuro and radio oncologists to be late radiation treatment effect and thought that they would resolve.

(Late February) MRI showed the enhancing nodule in right ventricle shrinking a bit, but enhancing area in temporal lobe cavity growing a bit. Still determined to be late treatment effect.

(June) : MRI – ALL HELL HAS BROKEN LOOSE. There are now another 3 large enhancing lesions – one in the right Frontal lobe, with a small one behind it, one in the Left ventricle (looks like a cherry sitting on the ventricle wall) and a much larger enhancement of in the original temporal resection cavity.

Needle Biopsy – a needle biopsy has just (yesterday) been performed on the right frontal lesion to get a better understanding of the makeup of the new lesions. We are currently awaiting the results and will also hopefully be getting a Caris or FoundationOne genetic testing on the sample.

The surgeon mentioned that he could already see an increase in size since her last last (less that 1 week prior). So this is a very fast growing tumour/s.

Proposed Initial Treatment

Her neuro-oncologist and radio-oncologist have suggested that she begin (as soon as possible) with CCNU + Procarbazine – and possibly Avastin for the swelling.

 Current Medications (all anti-epileptics):

- Epilim (Sodium valproate)

- Fycompa (Perampanel)

- Lamictal (Lamotrigine)

- Briviact (Brivaracetam)

- Frisium (Clobazam)

Suggestions

I would be extremely grateful if anyone can:

- provide their thoughts on the proposed treatment

- make any other treatment suggestions

- suggest anything that could possibly increase the effectiveness of the   
   suggested treatment

- point out any pitfalls or things to be aware/weary of whilst on the treatment

- suggest any promising potential trials or treatments anywhere in the world

- suggest any cokctails that they have used with this treatment that have 
  resulted in better outcomes + better tolerability

The rapid change from a fairly stable low grade astrocytoma really did catch us (and her doctors) off-guard and I would be very appreciative of any advice or suggestions that anyone could kindly offer.

Thanks to you all.

Ryan.

New Note:

Just today my partner was told that she has extremely low levels of Vitamin D. Strangely enough, she has been really craving oily fish for the last 3 months and has been eating smoked trout and smoked salmon almost daily - obviously not enough to build up sufficient levels. The 3 month craving of Vitamin D strangely coincided with the new lesions showing up and their extremely fast growth.

I wonder if dramatically increasing her Vitamin D level may slow the progression? She has started taking 4000 IU and intends to keep it up every day.

Can anyone comment on this level of Vitamin D, would you up it even further? And are there any caveats with regards to Vitamin D supplementation.

Also, it there a particular way to rapidly raise the levels in the blood?

Tom Wangerin - Cocktail Profile and Questions

Hi all,

Although this is my first post, I have been reading every minute of every day. Such an amazing wealth of information on here. I would appreciate any advice on our current course of action and opinions on our cocktail.

My dad was diagnosed with a grade IV GBM. He had surgery on 11/23/16 with 95% resected.

Lab Results:
MGMT Gene Promoter Methylation – Detected.
Percent of MGMT Methylation is 36.19%
IDH1/2 Mutation – Not detected
Positive for 1p Deletion

• Completed his first round of daily chemo/radiation on 1/19/17.
• Our first image was taken on 2/3/17. We had our first consultation with the UCSF Tumor Board (Dr. Butowski) on 2/7/17.
• Tumor had not seemed to grow in size any, but did morph into a new shape/area which is scary to see. Next image in 2 months.

Currently taking:
·       Dexamethasone (Decadron) – He is currently taking 4mg/day but we are doing what we can to wean him off. We have been told this will dictate whether we go on Avastin.
·       Eliquis – blood thinner - 5mg twice a day
·       Keppra – 500mg twice a day.
·       Bactrim (Antibiotic) – Original oncologist prescribed during chemo.

Supplements:
1:1 CBD/THC – Tincture drops in day, Oil at night.
Probiotics – Sibiotica (K-97)
Curcumin - Nutrivene Longvida 1000mg - 1x Morning 1x Night (1000-2000mg daily)
Fish Oil - Vital Nutrients - EPA-720mg, DHA-480mg per cap - 1x Morning
Boswellia Serrata Extract - Progena Meditrend – Currently taking (3) 333mg daily.
Melatonin - Vital Nutrients - 10mg/cap - 1x at Night (eventually will do 20mg)
Mushroom Extracts - Turkey Tail (Coriolus), Maitake D-faction, and Reishi each once a day.
Berberine - Vital Nutrients - 200mg/cap – starting with 1x day, soon 3/day.
Debating whether to add - Resveratrol and Green Tea Extract

Our NO was okay with all and suggested adding Cronaxal. I’ve struggled to find much convincing information out there, but I do trust our NO. Now the question is to use Cronaxal (expensive and high dosage) or get Sulfasalim (which Stephen ranked pretty high on his spreadsheet).
I read that this can benefit those that are NOT IDH mutated (which is us).

Genetic Testing
We are getting the tumor tested from Foundation One for more details – once we make sure there is enough tumor for them to test, and have some left for potential clinical trials. I’m keeping an eye out for EGFR, p53, VDR, HIF-1.
Any thoughts here?

Hoping for some advice in a selection of the following:

**Vitamin D3 – In some cases Vitamin D3 caused proliferation in some patients (Stephen W speaks of this: http://astrocytomaoptions.com/supplements/). Our NO was okay w/ Vitamin D3. Would checking his VDR receptor be of value for determining this, or is it safe (and potentially beneficial) to take 5,000-10,000iu daily regardless of tumor type?

I was very excited about a few of the prescription drugs below, but our NO was certain that none of them get past the blood brain barrier while taking doses safe for humans. We are still willing to give a few of them a shot, but I’m struggling to decide which combinations.

·       **Chloroquine Phosphate – (if overexpressing the EGFR protein or p53 status is unmutated) & **DCA - Sodium Dichloroacetate –(if HIF-1 is expressing) http://astrocytomaoptions.com/targeting-tumour-metabolism/
·      **Disulfiram – This drug looks like it has amazing potential.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=707

·       **Sildenafil & Celebrex: can work synergistically for both getting past blood brain barrier, anti-tumor qualities, and Celebrex potentially helping with a bit of edema.
http://onlinelibrary.wiley.com/doi/10.1002/jcp.24843/abstract

·      VT-122 (Etodolac & Propranolol) – with low dose daily TMZ schedule. This had great results. Any reason why more people aren’t doing this themselves?
(http://meetinglibrary.asco.org/content/151704-156)

·       CUSP9 – Looks like an amazing plan. I am yet to read of any results but I know many are starting to replicate this cocktail on their own.
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2408

Current Plan:

I.         TMZ Schedule – Because he is MGMT methylated it was an easy decision to go forward with the monthly TMZ cycles. All of our docs have insisted on the high dose 5days/month schedule rather than a metronomic schedule, regardless of whether EGFR is over expressed. Thoughts?
https://academic.oup.com/jnci/article/107/5/djv041/891259/EGFR-Amplified-and-Overexpressing-Glioblastomas

II.         Optune Machine – The UCSF board feels it’s not as beneficial as some of the studies make it out to be, and with it being such a pain to wear for the rest of your life… it’s not that easy of decision even with insurance coverage. I’m undecided here.

III.         Prescriptions with TMZ/Avastin - If you had to pick one prescription duo to take with TMZ and one prescription duo to take with Avastin to make them more effective which would you pick?

Thank you all for pitching in. This journey has been life changing, but manageable with the help you all bring.

My Mum's story so far (GBM - trying cocktail and immunotherapy)

Hi all,

I thought it was time to share my Mums story so far. This blog has been just so helpful and I am so grateful to Stephen and all who contribute to this so thank you.

I will try to keep this as brief as possible and focus on the important and maybe interesting bits for others going through this.

My Mum, Marilyn, aged 66 was diagnosed in July with GBM. Symptoms were; getting lost on her drive home from work (a drive she has done many many times), text messages were getting muddled, trouble feeling stable when walking down stairs and some speech issues such as forgetting the word for things. The first scan showed a very large tumour in her front left temporal region and a very small one further back on the left side near her speech and communication region. She is being treated in the UK where we are from but I live in San Francisco so I am back and forth a bit (trying to not get fired from my job but be home as much as possible to offer her and my Dad support). My brother is a great support too and lives in the UK.

After diagnosis, she had keyhole surgery on the larger tumour which was a success with 99% resected. We decided to leave the smaller tumour alone as there was a risk of her speech worsening and her symptoms were so relieved after her first op. The plan was to try to hold this smaller one in place with chemo and radiation. As she is being treated by the NHS she didn't get any tumour tissue testing as a standard which absolutely boggles my mind! I had to fight hard for it. The results from the pathologist got back to us insisting there was too much necrotic tissue in her tumour to be able to test for anything.

Mum started on a cocktail during radiation mainly of supplements but towards the end of the 6 weeks had added CBD oil and a few repurposed drugs from the Care Oncology Clinic; Metformin and Mebendazole. Celebrex has been impossible to get hold of for us even with two letters of recommendations from two different oncologists to give to our GP. However I am chasing a few more options now so there is still hope here.

After radiation/chemo her symptoms worsened significantly, in particular her sentence forming and some of her movements. We were told this was just a result of the radiation and to be expected so we were hoping she might start to improve again but in mid November things got so bad she was rushed to hospital. She could not talk and her right side movement was significantly impaired. She was given a high dose of steroids (after not being on any after radiation) as they found she had severe cerebral oedema. This was unfortunately caused by the smaller tumour growing significantly since her first operation. It had grown and a new one was forming next to it and very close to Mums motorneruone center.


Thankfully surgery was an option. She ended up having to wait nearly 5 weeks for the surgery as it was a 'really busy time of year'. It was a very long 5 weeks and Mum got back onto a cocktail during some of this and had been finding the CBD oil particularly helpful. She was not keen on taking THC but is very happy to take the CBD and feels brighter after doing so. The surgery happened on Christmas Eve and went as well as possible. The surgeon was a bit amazed/stumped to find so much necrosis, he said it "was all grey" and he could not see any live tissue. Normally there is some necrosis but he was really stunned to find as much as he did and felt that whatever she has been doing she should keep on doing that! I am not sure what to think here as her original tumour was also full of necrotic tissue so it could just be the nature of this GBM. It was interesting hearing how shocked the surgeon was though and how positive he felt that something was causing it to die.

This time around with the surgery we had asked again for tumour tissue testing but had no luck again due to the necrosis. We also decided to pursue immunotherapy at IOZK in Cologne with Stefaan Van Gool. Mum's tumour was frozen and shipped off to Cologne and they seem to think they can still build a successful vaccine with the tissue so that was some good news.

Mum's NO had wanted her to switch to PCV after she progressed during radiation but we felt it was too soon to give up on Temodar for a whole lot of reasons. With the number of scans she has had in the past few months we are able to see that a tiny bit of growth from her original resected tumour has stayed static indicating something is holding that in place. She started on her first month of the high dose Temodar a few weeks ago. Between days 5-10 of the month she will go to Cologne for her treatment.

The first NDV injection was done on Tuesday. They had her on a drip of Selenium, Vitamin C and Newcastle Disease Virus at the same time as having Hyperthermia treatment. She tolerated it well. She went back the next morning for the same again. So far my Mum and Dad have found the clinic to be really pleasant and they have been well looked after. Mum had a slight fever during the night on Wednesday but is good right now. Attached a picture of Mum undergoing the IOZK treatment...

We are adding and adapting Mums cocktail gradually but this is it below for next week. We have Cimetedine and Sildenafil waiting in the wings and are working on getting Celebrex and Minocycline too. We have not added the COCs other prescribed drugs, Doxycycline and Atorvastatin as there is not enough evidence of efficacy with these. We may consider adding DCA as well -especially as it is accessible although I am concerned about the potential side effects and being so far from home so often it is hard to only hand out the instructions and not be there to manage any potential symptoms.

______________________________________________________
First thing in AM         Lanzoprazole                      (x1)        30mg
______________________________________________________
Before Breakfast          Levetiracetum                    (x1)        500mg
                                     Wild Alaskan Fish Oil          (x1)        1125mg
                                     Selenium                             (x1)        200mcg
                                     Broccoli Sprout Extract       (x2)        1000mg

During/After                 Dexamathasone                 (x1)        2mg 
Breakfast                      Metformin                          (x1)        500mg
                                     Zinc                                     (x1)         50mg
                                     Boswellia (Wokvel)             (x1)         333mg
                                     Curcumin (Longvida)           (x2)        1000mg
                                     Ashwaganda                       (x1)        125mg
                                     Coriolus PSK                      (x2)        1200mg
                                     Honokiol (HonoPure)          (x2)         500mg
________________________________________________________
Before Lunch/Mid        Wild Alaskan Fish Oil           (x1)        1125mg
Morning                        CBD oil                                              100mg
                                      Pterostilibine                       (x1)         50mg

During/After                 Vitamin D3                            (x2)         4000IU
Lunch                           Green Tea Extract                (x1)         725mg
                                     Pterostilibine                        (x2)         100mg
                                     Boswellia                             (x1)         333mg
                                     Ashwaganda                        (x1)         125mg
                                     Mebendazole                      (x2)         200mg
 _______________________________________________________
 Before Dinner/Late      Flaxseed oil                         (x1)        300mg
Afternoon                     Curcumin                             (x2)       1000mg

During/After                Levetiracetum                    (x1)        500mg
Dinner                          Metformin                          (x1)        500mg
                                     Milk Thistle                         (x3)        450 mg
                                     Coriolus PSK                      (x2)         1200mg  
                                     Vitamin D3                          (x1)        2500IU
                                     Chloroquine                      (x1)         250mg
                                     Honokiol (HonoPure)         (x2)         500mg

_______________________________________________________
Bedtime                        Melatonin                           (x1)          10mg 


Does anyone know of any reason to not take a very high dose of Vitamin D3 for extended periods?
Whilst supplement shopping today I read the label on the back of one of the Vit D3 5000 IU bottles that said to only take once every other day and to be wary of taking for continued periods. I am not sure what side effects there might be and again I am sure whatever they may be are most likely insignificant compared with the potential benefits in this case.


Has anyone got any good methods for organising supplements? Any recommendations on pill organisers? I noticed Ben Williams uses them in the survivngterminalcancer doco. There are a whole range on Amazon. It makes sense to prepare a weeks worth ahead of time.

I am so grateful for this space to share and discuss. Thanks so much Stephen -I am not sure I can say thank you enough times!

Best wishes to all.

Alison

Edited to add IOZK cost breakdown:

Alfacalcidol D3

As part of his cocktail my husband has been taking 1mg of Alafacalcidol (vitamin D3) for almost two months now. Now I am not sure if this is the right dosage? It comes in capsules of 0.25mcg.