Thursday, 18 April 2019

Wednesday, 17 April 2019

Regarding Boswellia and Curcumin

Dear all,

My father just finished his first cycle of 5 days temodal and we took an early MRI. I wasn't surprise by the bigger size of tumor and edema because I guess it is too soon to judge. But the report shows "foci of hemorrhage" and although our NO. and some other drs said it is nothing to be worried, I am afraid of continuing with Boswellia and Curcumin long vida as they are apparently  blood thinner and might worsen the bleeding.
Do you have any suggestion? and have you ever experience such occasion? Shall I totally stop all these for ever and add more dexa and celebrex?  

Saturday, 13 April 2019

Artemisinin and Anti-Seizure Meds


Does anyone have a link to any studies regarding at what dosage Artemisinin is contraindicated for anti-seizure meds? I haven't been able to find any info on the dosing limitations specifically. Thank you :)

Thursday, 11 April 2019

PCV regiment and P-gp inhibitors

Inspired by Ben Williams who used Verapamil on BCNU and later on PCV regiment I was planning to use P-glycoprotein (P-gp) inhibitor like Verapamil during PCV chemotherapy.

Problem is that I can't find any research characterizing alkylating agents such as Carmustine, Procarbazine or Lomustine as P-gp substrates. Am I missing something?

Thank you.

Sunday, 7 April 2019

Cocktail for Yara’s father / help with drug side effects / 30% PD-l1 expression

Hello my dear friends and partners!

I had many doubts and I still have them despite of reading much.
And I decided to ask for your help at least.

My father had surgery 4 month ago. Chemoradiation finished 1 month ago. Left side of brain was damaged. He has Glioblastoma.

He has problems with speech and memory now.
That is why it is too hard to establish the cause of some uncomfortable and bad feelings after taking medicines and CAMs… He can not describe it correctly and can not remember when it was started for example…

---------He has no mgmt/idh1/braf/msi
---------He has 30% PD-l1 expression.
---------MRI shows continued growth (mono TMZ was not effective).

This month we started:
avastin+TMZ (5+23, 400 mg)

It is risky because TMZ did not worked well before. But I found it can do other work: reduce PD-l1 expression. And decided to use PSP(PSK) Oriveda together (6 pills =5 days with TMZ, 2 pills other days).

!) MAIN QUESTION: is this mechanism can work or not?

!) SECOND QUESTION IS: he is getting shakes. What can it be?  (inside based like fever). But temperature is ok. Blood pressure is pretty normal. Pulse is ok.
Problem is – he can not remember when it was started (may be after avastin). It was more than 1 time. He is hiding his condition may be…
And he sleeps much.

These supplements was added (after radiation/before or together with new chemo):
avastin (1 in 2 weeks) +TMZ (5/23)
++++++ melatonin 20mg only 5 days (or need to use all time?)

---------1) alpha lipoic acid (2x300=600)
---------2) curcubrain (1x400=400)
---------3) PSP(PSK) Oriveda (2x350 = 700  or 6 at TMZ days)
---------4) Carvedilol for pulse (1/2)
---------5) started to change carbamazepine (200mg) to keppra (250mg) – TOGETHER 1 week. Then more keppra less carb.

PS – keppra for unmethylated MGMT (still risk if TMZ not working)

Help me to connect his fever/shake with suppliments.
I can guess 1) it is avastin 2) keppra together carbamazepine 3) may be PSK/PSP… But may be you know bwtter?

Also he is taking (from the beginning)

---------metformin (1500)
---------Boswellia (2000)
---------D3 (4000)
---------Omega3 (1500)
---------Aspirine low dose

He has diabetes 2 type/hypertonia/

-----------What can I add or remove? (may be malatonin all days not only 5)? may be lower dose TMZ/ methronomic or replace TMZ with Irinotecan? (to not risk with combinations).
------------Is my combinations effective (TMZ+melatonin+PSP+keppra) with our mutations? (add/remove?)
------------What can be the reason of weakness and shake/fever?
------------Do you have link for Japan protocols (psk/psp)?
Thank you!

Friday, 5 April 2019

Recommendations on how to fight Insurance and Drug providers

Hello All

I wanted to solicit the group on ideas to fight the silly rules of my insurance and convince drug providers to support my doctors request.

Quick background:

This June will be my 4 year anniversary of GBM resection and Standard of care treatments.

Since then, I have had a couple of re-occurrences battled with additional resections and DNX2401 trial, including Keytruda infusions.

My last resection was in October of 2018 and since then I have been getting CCNU every 6 weeks, Keytruda every 3 weeks and completed 10 rounds of additional radiation.  Basically stable MRI's since the radiation.

after the last resection, my NO prescribed tragresso and Optune.  Both have been denied thru 3 rounds of appeals.  Also since I am still working I do not qualify for any financial assistance from Optune or lilly. 

So any good recommendations to battle the bureaucracy? My company does provide a Health advocate but they are only good for contacting the insurance company for status on appeals.  They do not provide any assistance with fighting for approval.

My NO and his team have been very helpful with submitting all the appeals and necessary supporting documentation but with out success. I am stuck in this grey area where I have completed the SOC and the only available treatments available are off label non FDA approved for GBM protocols that the insurance company will not pay for.

So thanks in advance for any recommendations.

Hi dear all,
Hope you are doing alright. I came with two questions. I've got my father CMV igg test and it is 17 (i.e. within borderline range).
I wonder if valacyclovir could work on an inopreable tumor of a 5mm size or it is only helpful on small size?
and more importantly, I found that apparently valacyclovir cannot be find here anymore, which is really frustrating. I know that you need prescription for that, but if you have any suggestion to provide it from a trustful source please let me know. I'll do anything to find it if it is if gbm alone is not enough, politics and other factors play role in this scary scene.
I wish one day we could all live in a better not know how people with more serious CMV situation are coping with this!      

Withaferin A (Ashwagandha) & TTF

Came across this study which may be of interest to Optune users. Stephen (and other scientifically literate folks) when you have time would be grateful for your thoughts about the science and its relevance to human application. Would also be interested to hear about people’s experience with Ashwagandha. Thanks!!

Thursday, 4 April 2019

Mislav's (netopoloit) Radiotherapy coctail

I've been following this blog for a while but since I haven't introduced myself yet here's a short backstory.

In July 2018 I was diagnosed with grade II astrocytoma in right precentral gyrus. I had a subtotal resection in October 2018, leaving some tumor tissue that was too close to corticospinal tract. Basic immunohistochemistry tests revealed the presence of GFAP and IDH (R132H), p53, ATRX mutations in resected tumor tissue.

My oncologist considers my tumor to be "high-risk" because of subtotal resection, me being close to 40 years old and, most importantly, the tumor tissue consisting of about 10% gemistocytic astrocytes. Because of this, we decided to start adjuvant therapy as soon as possible.

I should be starting radiotherapy in about a month (PCV chemo will be done later, separately).

I did a lot of research and this blog was a precious resource. I recently decided on a cocktail of medications and supplements to take during radiotherapy and would greatly appreciate any comments and suggestions on what else to include or what to exclude from the list.

This is a cocktail I intend to use during radiotherapy. I plan to use different cocktail later with chemo.

Important note: some of the points in "Reasoning" column may be based on weak evidence or may be speculative claims extracted from different sources. I didn't have time to compile all the sources of the information but if there are any specific questions in comments I'll be happy to post any additional links or papers.

List of Rx drugs:

Name Reasoning Note
Acetazolamide possible radiosensitizer;
carbonic anhydrase II (CAII) inhibitor.
Alfacalcidol promotes redifferentiation;
hedgehog pathway inhibitor.
Auranofin increases ROS;
inhibition of PI3K/AKT/mTOR axis;
inhibition/reduction of TNF, IL-6, CRP;,inhibiton of phosphofructokinase.
Celecoxib edema control;
COX-2 inhibitor;
PGE2 inhibitor;
carbonic anhydrase 9 (CAIX, CA9) inhibitor;
suppresses Wnt/β-catenin signaling.
Minocycline PARP inhibitor;
inhibits MMP-2 and MMP-9;
modulates phenotype of microglia;
disrupts CCL2 chemokine signaling;
STAT3 inhibitor;
NF-κB inhibitor;
MAPK pathway inhibitor;
hypoxia inducible factor 1 alpha (HIF-1α) inhibitor;
Akt/mTOR pathway inhibitor.
Sodium phenylbutyrate Histone deacetylase inhibitor (HDACi);
c-myc inhibitor;
urokinase inhibitor.
Disulfiram increases ROS;
possibly synergistic with Auranofin?;
proteasome inhibitor;
NF-κB inhibitor.
Memantine possible reduction of radiation-induced neurocognitive decline ?
Perillyl alcohol direct cytotoxicity;
possibly reduces endothelial-tomesenchymal transition;
mTOR inhibitor;
Ras inhibitor;
G1 cell cycle arrest ?
Prazosin limited evidence of direct cytotoxicity to glioma initiating cells;
Tamoxifen Still just considering use during radiotherapy. May be rendered useless by Celecoxib, a potent CYP2D6 inhibitor;
Will be used during and after PCV.
Ibudilast (MN-166) Just considering; No concrete evidence for use during radiotherapy. Limited evidence of benefits when used with chemo.
Itraconazole Hedgehog pathway inhibitor Not high on the list because of CYP450 interactions.
Mebendazole Will probably skip this one for now because of no evidence of benefits in combination with RT, also low bioavalibility.

List of supplements:

Name Reasoning Note
Boswellic acids edema control Downside: non-selective inhibitor of the major drug metabolising CYP enzymes 1A2/2C8/2C9/2C19/2D6 and 3A4 in vitro.
Glucans / PSK / mushroom extracts
Guduchi (Tinospora cordifolia) extract limited evidence of guduchi as differentiation agent and radiosensitizer
Honokiol (Magnolia bark, Houpu) autophagy promotor;
enhances ROS production;
Omega 3 / DHA High DHA/EPA ratio
Pterostilbene possible radiosensitizer
Sulforaphane possible radiosensitizer
Tetrandrine (from Stephania Tetrandra) Wnt/β-catenin inhibitor;
possible radiosensitizer.
Cannabis possible radiosensitizer
Epigallocatechin-3-gallate (EGCG) [from green tea extract] possible radiosensitizer
Garlic increases ROS;
NF-κB inhibitor;
HDAC inhibitor at high doses;
Luteolin increases ROS;
NF-κB inhibitor;
Silibinin (active component of silymarin from milk thistle) low dose during radiotherapy - could reduce ROS?

Happy Tumorversary to Ben Williams!

24 years ago on March 31 Ben Williams had his first GBM tumor resection.  Ben has been our family hero, helping us find our way thru the GBM maize.   He will forever be our inspiration.  Thank you Ben Williams for sharing all these years!!!

Stephen, will there be a new "Treatment Options for GBM & other Gliomas" update out anytime in near future ?

Tuesday, 2 April 2019

Clinical trial: IDH1 R132H peptide vaccine + avelumab (Germany)

A prior trial tested this vaccine (IDH1 R132H peptide vaccine) for gliomas with this IDH1 mutation.  The current trial is testing vaccine alone versus avelumab (PD-L1 inhibitor) alone versus combined vaccine + avelumab.

It is recruiting first recurrent gliomas of grade 2-4 with the IDH1 R132H mutation.

Open in Heidelberg and Mannheim Germany, and will also be open at several other centres in Germany.