Tuesday, 25 July 2017

Simvastatin positive evidence in an orthotopic GBM model

The study is called MYC-regulated Mevalonate Metabolism Maintains Brain Tumor Initiating Cells

This study constitutes in my view the first solid evidence that statins could be useful in GBM therapy. In accordance with my research, simvastatin was the statin selected which has better blood-brain barrier abilities versus some other statins, for example atorvastatin (see figure below).  The drug in this study was injected intraperitoneally rather than given orally as would be the case in humans, but at least they used a brain-implanted (not subcutaneous flank-injected) model with relatively recently created GBM cell lines (rather than the ancient U87).

Figure above from the study Statins as Neuroprotectants: A Comparative In Vitro Study of Lipophilicity, Blood-Brain-Barrier Penetration, Lowering of Brain Cholesterol, and Decrease of Neuron Cell Death by Sierra et al. Journal of Alzheimer’s Disease 23 (2011) 307–318.

ONC 201 or Avastin?

Stephen and all,
We are trying to decide between treating our son (recurrent glioma, H3 K27 mutant, mutations in ASXL 1 and PIK3CA among others) with Avastin +Irotican  or the new ONC201 trial. We tend to think that ONC201 is a better option. What do you think? Thanks!

Sunday, 23 July 2017

posts on DCA from the old cancer compass thread

I found some of the discussions on the old cocktails thread at cancer compass concerning DCA useful, including the two below.

April 19, 2015:
I talked with three different suppliers and one Canadian pharmacy about purchasing DCA. One company was rude, would not address my questions, and worse. Very evasive in who they were and quality issues. My selection came down to two providers and ultimately I went with pharma-dca. I chose this company because they claim their DCA is manufactured in the UK, not china like almost all other DCA. They addressed my questions respectfully and I liked one of the responses I received from them (see below). Additionally I was looking for someone else that had sourced their DCA through pharma-dca and found that Cheryl Broyles does.
Caveat emptor seems like a very important precaution here. I have not had their DCA independently tested. Therefore it could be excellent quality, it could be adulterated or not DCA at all. I am in no way suggesting their product is not what they claim, I am simply saying I have not had it tested. In my conversations with others using DCA, some source their product through pharma-dca as well and have no complaints. By the way, the other source I was inclined to trust was Certified DCA, but they were asking quite a bit more for their DCA. Below is pharma DCA’s response. If you are interested in certifiedDCA’s response to me let me know and I will post it.
Here is pharma-DCA’s response to me. 
 Hello Michael
Thanks for the response; Pharma-dca.com is part of the AWP group of internet companies.
We do however agree that the vast amount of Sodium Dichloroacetate for sale originates in China.
We have been concerned regarding this issue but as you will appreciate have no control over the purchasing by individuals who unfortunately have not the knowledge or realization of product source.
 AWP  for many years has had its own in-house fully equipped laboratory and routinely sample every batch of product produced.
 All our Sodium Dichloroacetate is produced within the UK to exacting standards; a typical analysis would be as follows:
All product is batch produced  and the batch number displayed on the product label for maximum quality control.
An inductively Coupled Plasma Mass Spectrometer offers the initial indication of the product quality, we have available if required a Perkins FTIR Spectrometer, a Hewlett Packard Gas Chromatograph plus other equipment.  Finally a sample of the finished product receives a quantitive analysis by titration.
 Only product that meets our strict guidelines is sent for packaging etc.
 Finally if you look at our website you will observe that we also produce potassium dichloroacetate, we have not seen this anywhere else including China.
 We welcome anyone to have our product analyzed on their own behalf

May 16, 2015
Some feel placing DCA in a freezer is important, most seem to feel just refrigeration is fine.  It is claimed the freezer keeps DCA fresher for much longer, but from a practical point of view, you will go through a 100 g bottle rapidly enough that it does not matter.  We keep it in the refrigerator.  We do not worry about with or between meals.  Benfotiamine is taken in the morning around the time DCA is taken.  Might be taken at the same time or at a different time, same with thiamine at night. 

Friday, 14 July 2017

My father's GBM

 My father was diagnosed with GBM on 4/15 and he had a total resection surgery on 4/17.  I've been researching pretty much non-stop every since.  I watched the surviving terminal cancer movie, read Ben Williams book, have been scouring the internet gathering as much information as possible and this is how I ended up here.  

Here's all the information I have on my fathers tumor and the treatment and supplements he is on to date:
Genetic testing: MGMT was not detected (negative) unmethylated
IDH1 and IDH2 were not detected (negative) as well
It is EGFR amplified - which qualified him for ABT-414 clinical trial.
He is currently in the trial and has some symptoms which lead us to believe he is getting the actual drug and not the placebo.  
He finished up the standard treatment of Radiation and Chemotherapy a few weeks ago.
He is taking Keppra and a PPI daily

List of supplements: Cannabis oil, 20 mg melatonin, 800 mg curcubrain, reishi and coriolus mushroom supplement, 500 mg Boswellia extract, 400 mg green tea extract, 200 mg resveratrol, 200 mcg selenium, 10000 IU vitamin D3, Hemp seed and flax seed oil.
Also drinking fruit and veggie smoothies daily.

These are the off label drugs that I recently received and plan on having him start in a couple days.
Disulfiram-125 mg a day for the first week, then 250 mg daily
Chloroquine- 250 mg daily
Celebrex- 200 mg twice daily
Metformin- 500 mg once daily, titrating up to twice daily, then 3 times daily
Doxycycline 100 mg twice daily
Propranolol 60-80mg daily
DCA 5mg/kg per day, titrating up to 12-15mg/kg.
LDN (low dose naltrexone) start with 2mg nightly titrating up to 4.5mg

I have a few questions:
1.How does the dosing and schedule of the off label drugs look? Anything I should add or subtract? 
2. I know Disulfiram and DCA can cause neuropathy, should they not be taken together?
3. Should the green tea extract pills be avoided while on DCA?
4. The doxycycline I have is Dox T-SL (Doxycycline 100 mg / Lactic Acid 5 billion spores)  
It says "DOXT-SL contains Doxycycline along with 5 billion spores of lactobacillus sporogenes."
Would the lactic acid cause a problem?
5. Most of the research I've done says statins are beneficial, but I've also an article saying they should be avoided.  Should they be used or avoided? 
If he does take the Celebrex, any recommendations on dose?
6. The Naltrexone pills I have are 50 mg.  I've seen people dissolve them in 50mg of water and then use a syringe to suck up desired amount in mg.  Is this advisable?  Some people say this will cause inconsistent doses, but I don't know another way.
7. I've read that since his GBM is unmethylated and EGFR amplified that a metronomic chemo scheduling would be more beneficial than standard chemo treatment.  We meet with my fathers oncologist next week to take a scan and discuss the future game plan.  Does anyone have any recommendations on how to try and convince his dr. to prescribe the metronomic dosing schedule.

Any help or suggestions would be greatly appreciated.  Like I said, I've been doing a ton of research and sometimes it seems like the more I do, the more confused I get.  

Saturday, 8 July 2017

help with Dex effects

my husband had a second recurrence at the end of May.  Further surgery is not an option (he had awake craniotomy with Gliolan in February for first recurrence, so we were very disappointed that it came back so quickly).  He has been on 16mg per day of dexamethasone since May 30.  We are trying to make the most of every day but the fatigue is extreme and he has weakness and visible muscle wastage in his arms and legs. Does anyone have any tips please on how to counteract the fatigue? He is 47, first diagnosed August 2015.

Any help much appreciated.

Friday, 7 July 2017

Updated statistics from Duke's modified poliovirus trial for recurrent GBM

  • As of 2/01/2017, 52 pts were treated on study (1 each at DL1 and DL3, 7 at DL2, 2 at DL4, 4 at DL5, 24 at DL-1 and 13 at DL-2)
  • 20.8% of pts remain alive at 36-month post PVSRIPO infusion, compared to 4% of an historical control.
  • Four pts remain alive more than 22 months post treatment without having received any additional intervention following PVSRIPO at 57.5+, 56.4+, 27.9+ and 23.2+ months.

An important thing to keep in mind is that the patients in this phase 1 trial were treated with various doses of the virus.  We can expect future trials that move forward with the approximately optimal dose to have better overall results than this trial.  The first patient in this trial is now 5 years in remission.

Sativex (THC + CBD) plus temozolomide for recurrent GBM

This was mentioned in the comments a while back (February), but I feel these findings are significant enough to have their own post.

The original press release by GW pharmaceuticals came out on February 7 (click here).

The data was also published for the 2017 ASCO conference (click here).

"Median survival in the placebo group was 369 days, and > 550 days in the CBD:THC treatment group (NS) and 1 year survival was 83% and 56% in the CBD:THC and placebo groups, respectively (p = 0.042). "   

Even with the small numbers of patients (12 patients in the Sativex + TMZ group, 9 patients in the placebo + TMZ group), the difference in survival at one year still managed to achieve statistical significance.

Sativex (nabiximols) is available in Canada and Europe. 

Complete responses to Toca 511 for IDH1 mutant gliomas

This was an abstract from this year's ASCO conference.

Durable complete responses observed in IDH1 mutated high grade glioma at first recurrence undergoing treatment with Toca 511 and Toca FC  (click here for the abstract)

"All 4 IDH1 mt patients treated at 1st recurrence had CRs [complete responses]"  !

Thursday, 6 July 2017

Is SWI part of standard MRI imaging?

I recently read that SWI can reliably determine regrowth from pseudo-recurrence. If this is the case why are there so many concerns about pseudo-recurrence? Is SWI not used standardly? Does it have pitfalls? Does it require use of contrast agent? (I haven't had MRI with contrast yet, due to pregnancy, so I'm wondering about "establishing a baseline" from which to measure my tumour going forward.)

Monday, 3 July 2017

IDH1-inhibitor drugs?

Hello all,

I've not fully understood how mIDH1-inhibitors work? I know they reduce 2-HG levels but does that lead to tumour regression, or is there some other mechanism simultaneously?

I've been looking into different mIDH1-inhibitor trials, but have doubts if they work as monotherapy?


Getting Second Opinion - Planning for recurrence

Hi all,

My Dad was diagnosed in Nov. 2016 with GBM (MGMT methylated, Positive for 1p Deletion, NOT IDH1/2).

He has completed standard chemo-radiation and is about to start his 6th cycle of monthly TMZ. We have had (2) Avastin infusions so far (hoping to keep this as minimal as possible) to help us wean off decadron, now down to 1mg per day.

As of our last MRI my Dad is considered "Progression Free - Post Avastin".

We are seeing Dr. Butowski at UCSF. He is very intelligent and has been willing to discuss our cocktail decisions. He simply states what is safe, his belief of what works and what does not based on research, and then let's us make our decision.

We do not want to switch NO's, but so far in this journey he has not been interested in any clinical trials (for my Dad) happening anywhere on the West Coast. He feels we stick with TMZ and sporadic Avastin infusions until (statistically likely) a recurrence appears. At that point we make a plan based on what is found...

I don't feel comfortable with this plan, I want to stay ahead of this. I want to start reaching out to various clinical trials of any phase and see what makes the most sense. Dr. Butowski leads much of the research at UCSF and has seen many trials do nothing and/or have very negative side effects on patients so he is more cautious than other NOs. I know this is something to be thankful for, but also very frustrating.

I would like to setup a consultation with another NO from a leading brain tumor center anywhere in the world to sit with and run through our situation for as long as I can get. I would love if members from around the world could list NO's they admire and respect.

Might actually be worth developing a shared Google Sheets for Stephen W Library listing all NO's with forum members ratings/opinions.

Any advice is appreciated.

Thank you and never give up


Oakland, California