Adderall for focus/energy

The great puzzle of dosage and meds. My husband has been on Provigil for about a year. He took 100mg morning, 100mg at lunch time but with little effect. I have asked Greg's neuro-onc to switch to Adderall, and she has. As of Sunday, Greg is now taking 10mg of Adderall XR. Some people in various blogs talk about a light switching on, increased energy and focus, I have yet to see much change. As background, Greg is 62 yr-old, with GBM, right frontal lobe, diagnosed May 1, 2015.  No resection possible. He has been taking the Stephen Western/Ben Williams cocktail since about October. Greg is now about to begin Avastin this Wednesday with the hope of reducing edema since nothing else seems to work and that includes cannabis oil, curcumin, etc. Sorry, two different subjects but possibly related?

Cusp9?

Anyone know when CUSP9 is going to start?

Optimising cancer immunotherapy

Interesting information on immunotherapy

http://emjreviews.com/wp-content/uploads/Optimising-Cancer-Immunotherapy-Challenges-and-Opportunities.pdf

Towards precision medicine-based therapies for glioblastoma

Interesting article.  Thoughts?

https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2908-7

Coley's Toxins and CHIPSA

I had heard about Coley's Toxins through this NPR article:

http://www.npr.org/sections/health-shots/2015/12/28/459218765/cutting-edge-cancer-treatment-has-its-roots-in-19th-century-medicine

and had forgotten all about it until someone mentioned it in a group that I'm a part of, specifically, the version being offered by CHIPSA in Mexico:

http://chipsahospital.org/coleys-dendritic-therapy/

The video is actually factually correct up until the service-selling portion. I was wondering if anyone had any experience with it and how they felt it rated against Dr. Raymond Chang's offerings here in my hometown of NYC?

Anyone have any experiences to share?

Intranasal delivery

This post is a response to Joanne's post about the cerebellum, as I wanted to include a visual.  For tumors in the cerebellum, the method of delivery might be the most important factor.  According to one study,

"The cerebellar uptake of IN delivered neurotherapeutics is found to peak at 12h rapidly declining by 24h. IP delivery does not exhibit peak cerebellar uptake at any particular time point, rather it is observed to be at the same level at all time-points. Cerebellar uptake of neurotherapeutics after IN delivery is ~5 ± 2 times greater than that after IP delivery"

In other words intranasal delivery results in far higher drug levels in the cerebellum compared to intraperitoneal injection, which is the usual method for delivering drugs to lab animals.

Click on image above to enlarge.  The 4 lines at the top represent levels of therapuetics (including curcumin) in the cerebellum after intranasal delivery.  The 4 flat lines on the bottom are the same therapies after intraperitoneal injection to mice.  Quite an impressive difference.

From the study: Brain Uptake of Neurotherapeutics after Intranasal versus Intraperitoneal Delivery in Mice

The question from here is which therapies are formulated for intranasal delivery.  Perillyl alcohol and chlorotoxin (scorpion venom) are taken this way, though neither of them are easy to access.  As we've discussed recently there are curcumin nasal sprays on the market, though I haven't seen any clinical research published with them.

http://store.bioponic.com/curecumin2.html

Let's make this the "intranasal therapy" thread.

Cerebellum

Trying to work out if there are any cocktail drugs that may help if recurrence is diffuse and has occurred in the Cerebellum,(original site was left temporal lobe.)

Any thought greatly appreciated.

Coffee intake and glioma risk

Interesting new study that found:

"a significant inverse association between coffee consumption and brain tumor risk in both total subjects (≥3 cups/day; HR=0.47, 95%CI=0.22-0.98) and in women (≥3 cups/day; HR=0.24, 95%CI=0.06-0.99), although the number of cases in the highest category was small. Furthermore, glioma risk tended to decrease with higher coffee consumption (≥3 cups/day; HR=0.54, 95%CI=0.16-1.80). No association was seen between green tea and brain tumor risk."

3-bromopyruvate questions

I was recently asked what I know about 3-bromopyruvate.

It certainly has all the preclinical rationale and demonstration of efficacy needed for clinical trials. My two main questions about it would be:

1) where a person would get it in a formula safe for human use.

"Hence, it is suggested that PET scan positive cancer types may be benefited after treatment with a patented and proprietary formulation of 3BP. It is worth noting that unformulated 3BP may be harmful in some cases."

"The patient was treated immediately via TACE with specially formulated 3BP (patented and proprietary)..."

http://www.ncbi.nlm.nih.gov/pubmed/22328020
The first author of this study quoted above is the person responsible for developing 3BP as a cancer treatment.  I'd recommend the book "Tripping over the Truth" for the highly interesting inside story on that.
http://beyondfunctional.com/review-tripping-truth-metabolic-theory-cancer/

2) who would administer it and how?

I've not heard of oral administration of 3-BP, it is given intravenously or directly injected into tumors. In the only in vivo glioma study I'm aware of, the 3-BP was inserted into the brain in the form of a biodegradable wafer (not unlike Gliadel).
http://www.ncbi.nlm.nih.gov/pubmed/25053853

In the most famous in vivo study of 3-BP, the 3-BP was also applied intratumorally to hepatocellular tumors.  http://www.ncbi.nlm.nih.gov/pubmed/15465013

For brain tumors, it's not even clear if intravenous administration would be sufficient.  There must have been a reason these animal studies applied the 3-BP intratumorally rather than the more common systemic method of intraperitoneal or intravenous injection.

Finally, since no phase 1 trial has been conducted, we have no knowledge of what the proper dose and safety profile would be for intravenous or direct application into the brain.  These are all significant problems that need to be overcome before 3-BP can become more commonly used for brain tumors.

CO Consultants

We are getting ready for a visit to Husband's NO on Aug. 31st, gathering as much information as we can to take with us.  If his scan shows any GBM growth, we are going to ask about adding a couple more "bombs" in his carpet-bombing arsenal.  (The information we get here is so very, very valuable.  Many thanks to Stephen for starting this blog.  You are a missionary from God!)

My question concerns CO Consultants...can anyone recommend one that has helped them personally?  I see Aunt Zelda's, Miriam's Hope, and Green Health Consultants and know there are others out there.  Since Texas is a compassionate use state for epilepsy only, I guess we will have to fly to another state to get our card, but even then, I have no idea how we'll get the CO regularly.  We need to talk to someone who knows about this better than we do.  Help?

zinc + temozolomide regresses U87 GBM in mice

From a new study in Oncotarget.

The green line in the top graph shows tumor regression in mice treated with zinc + temozolomide, but not with temozolomide alone.  The bottom graph shows tumor volume at 7 time points in each of the groups (no tumor at the final two time points in the TMZ + zinc group).  

This was an orthotopic (intracranial) tumor implant model, with U87 (p53 wild-type) GBM cells, and TMZ and zinc were administered orally. The study does not say the dose of zinc used, and does not address whether zinc is normalizing the protein conformation of p53 in the U87 cells.  A prior publication showed that U87 cells had mostly mutant-type dysfunctional conformation of the p53 protein, even though there was no p53 gene mutation, due to high expression of metallothionein which steals zinc from the p53 protein.

Glutamate?

Hello,

there hasn't been much written about the role of glutamate in gliomas, so I was wondering if anyone had looked into it before? It caught my attention some time ago when someone posted a link to "medical food" Cronaxal, which "is a combination of oxaloacetate and ascorbic acid (vitamin C). Oxaloacetate reduces Glutamate levels in the brain in multiple laboratory animal tests.  Glutamate overproduction is directly tied to the growth of malignant gliomas, their invasiveness, and their ability to destroy neighboring brain tissue.  Patients with Glial Tumors have an impaired capacity to metabolize glutamate due to the high amount of glutamate produced by the tumor itself.  Oxaloacetate helps to metabolize glutamate to alpha-ketoglutarate."

Anyway, search on pubmed does return some hits on glutamate and glioma, for example Glutamate and the biology of gliomas (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107875/) where it states: "Glioblastoma tumors release Glu to enhance their highly malignant behavior, and that Glu release via system x_c^- and the excess extracellular Glu this system imparts a survival advantage by promoting resistance to apoptosis and by promoting glioma proliferation and invasion. In fact, the invasive nature of gliomas enhanced by Glu release is one of the most important limitations to effective disease control; experience demonstrates that more than 80% of glioblastoma recurrences occur within 2-3 cm of the original resection cavity. Successful treatment of malignant gliomas requires recognition of Glu and its receptors as potential targets and novel approaches modulating their influence are needed to improve upon existing ineffective therapies."

At the end of the article there are some suggestions for targeting glutamate with repurposed drugs, but I also found some supplements that could do that in some degree (like theanine, N-acetylcysteine and glycine). Anyone tried this approach to complement the cocktail?

 

Treatment Options for Glioblastoma and Other Glioma - 2016

I'm pleased to announce that the annual Ben Williams Treatment Options update was published today on the Virtual Trials website.  I've inherited the annual updates from Ben, and had been working on this for the past few weeks.

  https://virtualtrials.com/newsarticle.cfm?item=6140  (for Al's commentary and link to the PDF)

Direct link to the PDF here

My brother has been doing TMZ 5/23 for over 18mths. We are wondering about changing the dose to daily low dose to try and avoid the fatigue etc that he has for that week. Would low dose be as effective? He is MGMT methylated.
Thanks, Lisa

First MRI and follow-up

Hi,
My father is due on Tuesday for the first follow-up after radiation and two rounds of monthly 5/23 high dose TMZ.

No MRI was taken after radiation but prior to monthly TMZ. I asked the NO if it wouldn't be a good idea to have an MRI taken one month after the RT, but she said it was too early to see the effects of the radiation, and besides it simply wasn't their way of doing things.

So this will be the first MRI to compare to the post-op scan taken the day after surgical resection of the tumors.
Since he's MGMT unmethylated I suspect the TMZ will not have had that much of an effect, and thus the question: What to do if the scan shows progression or recurrence?

Continue the monthly TMZ or suggest something else - carboplatin, irinotecan, re-operation if possible, try the german clinics, something else?
I guess CCNU wouldn't really be any better, since it works the same way as TMZ?
What would be the least bad/unpromising "salvage therapy" - Stephen?

I had a quick check on clinical trials in Sweden but nothing targeting recurrent tumors.

Father's profile:
* EGFR positive/staining (but unknown if EGFRvIII mutated or not)
* IDH1 R132 negative/unmutated.
* Weak p53 staining (likely unmutated p53)
* No loss of 1p or 19q.
* MGMT unmethylated (9% methylation)

Thanks,
Peter

Hepatitis C

I would love some feedback about whether we should try and tackle my husband's Hepatitis C. He is not eligible for almost all clinical trials because of Hep C. My concern is using drugs like Epclusa or Harvoni could make things worse for him. Trying to get a liver specialist & his neuro-onc on the same page is difficult. Any feedback or experience would be most welcome. 

More progressive NO in Los Angeles

All -

I was just cleaning out my pile of notes from the UCLA Brain Tumor Conference last March.  I spoke with Dr. Albert Lai albertlai@mednet.ucla.edu;  310-825-5321 after his lecture and he said that he generally will prescribe something for GBM if the patient asks about it.  I know some of you ran into hurdles getting a NO who would give you some of the cocktail meds.  I believe Dr. Lai is open minded.  Also I had asked about seeing my Dad via Skype as we are in Seattle.  He said that he had never done that before but it may be an option.

Just wanted to share that with you as I know some folks have had trouble with their Oncologists.

Best.
Annie

SMPF Therapy V Novocure.

Any thoughts on which may be more effective?
I know Novocure has had more trials and data but as it needs to be used for
such a large part of the day on a shaved scalp my daughter isn't keen.
The small amount of information I have on SMPF, which is carried out in Bangalore seems quite promising.

Niclosamide

I was discussing options with Dr. Hercbergs (T4 suppression treatment) and he brought up Niclosamide.  A quick internet search brings up some interesting information.  Anyone familiar with this?

mTOR inhibitors

Does anyone have any knowledge of mTOR inhibitors and availability?

I am looking into them as a target for MYCN amplification due to the
 H3F3A G34r mutation that my daughter has.

We have today had recurrence confirmed in inoperable areas and are trying to decide what may be the best way forward.
There don't seem to be a lot of options with this mutation.