Sunday, 17 March 2019

H3K27M diffuse midline glioma

Hello everyone!

My wife (30 years old) was diagnosed diffuse midline glioma (H3K27M).

The story so far:
27/10/2018 MRI, evidence of brain tumour in brainstem.
11/11/2018 stereotaxic biopsy. According to the results of histological examination: diffuse midline glioma WHO IV H3K27M. H3K27M immunostain is strongly positive.
27/11/2018 MRI, tumour increased as well as brain swelling after biopsy.
03/12/2018 - 06/12/2018: chemotherapy course. Temozolomide (280mg) + Carboplatin injection (300mg).
12/12/2018 VP shunt placement.
29/12/2018 chemotherapy course. Temozolomide (250mg) + Bevacizumab injection (400mg).
09/01/2019 MRI, short decrease of tumour size.
10/01/2019 chemotherapy course. Bevazicumab injection (400mg)
25/01/2019 chemotherapy course. Bevacizumab injection (400mg)
08/02/2019 chemotherapy course. Temozolomide (100mg) + Bevacizumab injection (400mg).
22/02/2019 chemotherapy course. Bevacizumab injection (400mg).
27/02/2019 end of radiotherapy treatment. Truebeam, 31 session, 55,8gr.
07/03/2019 chemotherapy course. Bevacizumab injection (400mg).

Also we made Foundation One Cdx genome analysis. In the accordance with the results:
Microsatellite status - MS stable
Tumor Mutational Burden - TM-Low (5 Must/Mub).
Gene alterations:
CD274 (PD-L1) amplification - equivocal
FGFR1 - N546K
NF1 - Q1993
PDCD1LG2 amplification - equivocal
H3F3A - K28M
JAK2 amplification - equivocal

We have ended radiotherapy about three weeks ago and we must decide what to do next. Our chemotherapist in Moscow suggests to continue taking Bevacizumab every two weeks with no additional treatment.
We are planning to do MRI next week (22.03.2019).

1) Will the immonotherapy be effective in our case? We have contacted IOZK and Verita Life clinics in Germany. There is also an option of immunotherapy in Moscow.

2) Are there any promising ways (clinical trials for example) of treatment of H3K27M?

3) My wife took dexamethasone (8mg daily) for 3,5 months. We quit dexamethasone for three weeks now. Now she has moon face and big belly. When does usually these symptoms go away?

Thank you so much and best wishes to everyone,
Alexander 

Friday, 15 March 2019

Diffuse glioma of the brain stem

Dear Stephen, dear all!

I ask for advice for my friend, she has a child (8 years old). Diffuse glioma of the brain stem (diagnosed 2015).
March - April 2015 received a course of radiotherapy 54 gray. No chemotherapy.
In January 2017, a new tumor on MRI - less than 5 mm (doctors decided just to observe). In December 2017, MRI showed almost 7 cm tumor.
On January 24, 2018, a biopsy was performed - midline glioma, mutation H3K27M.
March-April 2018, repeated radiotherapy course of 54 gray. No chemotherapy.
November 2018 negative dynamics on MRI.
Mutations:
ATRX - contained in the cores
H3.3 - Mutations detected in the H3.3_K27.M gene
IDH1 - no
p53 - accumulation in nuclei (70% of cells)
1) What can be done in this situation (third radiation therapy, chemotherapy, avastin, dendritic cells, viruses)?
2) Please advise promising clinical studies or clinics that deal with such cases?
3) What drugs could be added due to his mutations?
Thank you!

Monday, 11 March 2019

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.

Sunday, 10 March 2019

High Dose Valganciclovir for GBM

Hello,
Re: Valganciclovir
Has anyone followed the Sweden GBM study's dosing on Valganciclovir while using the Care Oncology Protocol? If so, did you isolate the Valganciclovir to be taken on its own for the first 3 weeks, or did you have no issues with using the 4 Care Oncology drugs while in the 3 week high dose loading period of Valganciclovir?
We just received our Valganciclovir and our Care Oncology shipment and wondering if should wait 3 weeks before introducing others into the protocol.
Thank you!

Friday, 8 March 2019

Advices before radiation therapy

Dear Stephen, dear all!

My mother had an operation (summer of 2018), not completely removed. There was no radiation therapy. Then she took TMZ 5/23 and Avastin, after 7 courses the tumor began to grow.

Next week Mom starts radiation therapy.
In this connection, I have a number of questions.

1) If TMZ ​​5/23 does not work, can we try the metronome scheme for the period of the radiation? Or is it better to change the medicine? The tumor is methylated.

2) What do you think about platinum drugs with TMZ?

3) Has anyone heard of Vidaza? Our doctor says that in Germany they use it in protocols with glioblastoma.

4) How long before radiation therapy should she take thc/cbd oil so that it works as a sensitizer? How much ml? Or we should devide it into 2 doses?

5) Which of the following is better not to include in a cocktail during radiation therapy: (and what is better to add?)

  • Coriolus versicolor
  • Maitake D-fraction
  • Selenium
  • Chloroquine 
  • Celebrex 
  • LDN 
  • Aged garlic (What is the dosage of garlic???)
  • Omega 3 
  • Zinc 
  • Prozak
  • DCA – 25 mg/kg х 2 times
  • Milk Thistle 
  • Dandelion 
  • Wobenzim
  • Berberine 
  • Boswellia WokVel 
  • Pterostilbene 
  • Metformine
  • Depakine chrono 
  • Probiotics
  • THC/CBD


Please help me! Thank you!

Thursday, 7 March 2019

Seeking medical marijuana providers

Hi all,

My brother was diagnosed with GBM 8/2017.  He had resection and good response to SOC plus our own added cocktail.  He has been taking THC / CBD but sometimes has issues tolerating and finding the right balance.  Has anyone worked with medical marijuana providers that treat brain cancers.

We are in Boston but willing to travel.

Kind Regards,

Jenna
OK! finally I found a trial in Iran and apparently they are working on Zika and Mesenchymal cells of patient...I will inform you if I find more about. They said two of their patients are alive after 4 years (I don't know how many were there though!?). It seems that the trial is even free.
Well I don't want to be too exited before knowing much about it...
I found that there were some posts on Zika here, but I would like to know more of your opinion about it. Shall we go for it as it is the only one going on here? do you know which type of tumor might reply better to this method?
Do you recommend metronomic Temodal with it? (Since it is going on by a university, I guess they are more open to opinion)
Thanks   

Sunday, 3 March 2019



I am quite ashamed for sending this much posts and I promise to make them less. Just want check the cocktails now that we are ending the radio+tmz parts and ask what should be replaced in the following one month off. 
My father is taking these along with 120 TMZ and most of these had been added after the blood test:

6 boswellia wokven
3 longvida
1 melatonin 5 mg (this might become 2)
2 milk thistle (150, standardized to 80 %)
2 metformin 500 (i.e 1000 mg)
3 ranitidine (Just to support  his weak stomach. He took Cimetedin 600 mg for more than a week and then I was afraid...because of Metformin)
1 valporate sodium 500 mg
2 cotrimoxazole (as you guess prescribed by ON)
Still damn 4 mg dexa

He would makes suicide if I add even one more pill now, so I will wait for replacing kepra with valproate and maybe getting rid of cotrimaxazole would give us more room..

His blood test 10 days ago shows these factors to be low:
 W.B.C 3.7
R.B.C 3.54
HGB 12.4
HCT 35.7

1- Do you think adding this MRM Veggie protein is of any help or is it more harmful? So far, that’s what I could find here but if you could suggest any powdery thingy that include those rare blueberry’s stuff, etc. I would be really thankful and I will order it asp.  

2- I will try to add vitamin d3 and maybe a bit of Iron thingy after finishing this round. something else you recommend? 



Friday, 1 March 2019

1st Recuurent Help please







Hi All

I hope All are good

My mother Diagnosed with Glioblastoma 2/8/2018 
The previous Mri on 30/12/2018 Showd that there is two new tumors

The first one 3.4 x 2.5 x 3.5 cm the second one nearest the first one but it is small 0.7 cm

We started Daily Temodal on 08 /01/2019 with Drug cocktail

Temodal 60 mg daily
Celbrex 400mg daily
Chloroquine 250 mg daily
Prozac 20 mg daily
keppra 2000 daily
Depakine 1000 daily
We start DCA for second time before 6 days 500 daily
And all Supplements 


The latest Mri on 20/2/2019 Showed

The biggest tumor shrinking to 2.3 x2.5x3.5cm
the smallest one increased from 0.7 to 1cm

What are you suggesting now going with SRS + Avastin Or continuing with Temodar and adding the remaining drugs?
Why one tumor is shrinking and another one increasing?
Is there any benefit if we continuing Temodal??
Is there any chance for second surgery after 7 months of first surgery?she is walking ,eating,doing every thing normally without any problem..
Please help 
Thanks
Modar

Experimental surgery




I need some information for possible surgery of my father … I am quite sure that partial surgery alone cannot help him so much. So I would only insist on surgery if I can find some alternative way of doing that (I mean those which can be done mostly by a crazy, brave surgeon in Iran and does not include some dreamy technology, etc.). I need to be prepare and I would only use it as the last shot.

 For the start, I’ve heard about two patients of DR. John Boockvar who survive for a long time. If I understand correctly, this includes micro cut of BBB, using mannitol to keep them open and then Avastin has been sprayed directly and the result was wonderful. I wonder why it has not become the standard? Or is it now more common there and I am just not aware?
Any other successful experiments that give me the courage to go for finding such surgeon are highly appreciated. And sorry if it is not directly related to cocktail, I promise not to continue this thread for too long.

Ibudilast for a cocktail?

Ibudilast was approved in Japan in May 1989.
In 2017, the drug was approved in the EU.

https://www.ncbi.nlm.nih.gov/pubmed/30814573
https://www.nature.com/articles/s41598-019-39427-4

In vivo, combined ibudilast and TMZ treatment of a patient derived xenograft (PDX) model resulted in significantly longer overall survival. Our findings have significant clinical implications for people with GBM. Since clinical trials involving ibudilast have shown no adverse side effects and the drug readily penetrates the blood brain barrier, treatment of GBM with this combination is clinically achievable.


MIF inhibition in combination with ibudilast and TMZ treatment results in longer survival in vivo. Tumor-bearing mice were treated with indicated drug combinations with the following doses: Ibudilast (5 mg/kg); Ibudilast (20 mg/kg); TMZ (10 mg/kg); Ibudilast (5 mg/kg) + TMZ (10 mg/kg) and Ibudilast (20 mg/kg) + TMZ (10 mg/kg). There were n = 8 mice in all groups. All treatments ceased by day 100.

At 43 days post-implantation, large tumors were present and treatment commenced. When all vehicle-treated mice reached their neurological endpoint (median survival 100.5 days), treatment was stopped. The treatment of tumor-bearing mice with ibudilast only resulted in inferior median survival times compared to the vehicle-treated mice (89 days and 97.5 days respectively) (Fig. 5A). A survival advantage was observed with mice treated with TMZ alone (median survival: 105.5 days compared to 100.5 days; LogRank p = 0.055). Combined treatment resulted in significantly longer survival. Mice treated concurrently with ibudilast (5 mg/kg) and TMZ (10 mg/kg) displayed a median survival of 114 days (p = 0.005) while the combination of ibudilast (20 mg/kg) and TMZ (10 mg/kg) resulted in a median survival of 111.5 days (p = 0.014).

P.S. The authors of the study write about a significant improvement in the survival of mice, but we see that the best survival in the treatment with a combination of drugs is 114 days versus 105.5 days in the treatment with temozolomide alone.

Wednesday, 27 February 2019

When to begin adjuvant tmz?



Dear all,
Believe or not, we are going into a long holiday here and it does not seem anybody would inform us what to do for the next month or so! My dad tmz + radiotherapy sessions would end within two weeks.
I urgently need your help so I can somehow catch someone before they all disappear in their holidays:

-          1- Is there usually a break before starting the adjuvant tmz? if yes, for how long?
-        2-  From the beginning of the treatment we never had a MRI, when should it be done? Since there was no surgery, could they decide whether tmz is the best choice now, or it is usually after finishing 6 or more cycle of tmz to say?
-          3- He is now on 4mg dexa and 3 wokvel boswellia (I’ve just randomly chosen these dosage and I have no idea if it is enough or not!), how and when should I start decreasing dexa?

BTW, he is loosing his right visual field (left temporal) ...dose it only means progression? his memory is getting better though I guess...

Any thought or experience is highly appreciated, thanks.

Time to say goodbye

Hi everyone,
it's been a while since I have posted anything. The worst has happened and my Dad passed away in September (55 years old). We spent his last three months on hospice care and watching him die was the hardest part. I miss him so much and the only positive thought I can come up with is that he doesn't have to suffer any longer...

My Dad was diagnosed with an inoperable glioblastoma (corpus callosum) in December 2015. He was told he had three months to live but he proofed all his doctors wrong!

An important part of his cocktail was methadone and we're sure that it played an important role in keeping him alive for almost three years. He had switched Temodar to the metronomic scheme, so we have many unopened boxes at home. We would feel very bad if we had to throw them away, so I'd love to send them to anyone who really needs them - just let me know!

Thank you so much for this blog, Stephen. It has been extremely helpful.
And I wish everyone all the best, keep fighting!!!

Take care
Steffi

Monday, 25 February 2019

IDH1 status

Can a tumor originally labeled as IDH1 mutant become IDH1 wild type in the event of a recurrence?

Sunday, 24 February 2019

Idebenone as potential anti-cancer agent.

Any thoughts about this?
https://www.ncbi.nlm.nih.gov/pubmed/30602587

Repurposing of idebenone as a potential anti-cancer agent.

Abstract

Glioblastoma (GB) represents the most common and aggressive form of malignant primary brain tumour associated with high rates of morbidity and mortality. In the present study, we considered the potential use of idebenone (IDE), a Coenzyme Q10 analogue, as a novel chemotherapeutic agent for GB. On two GB cell lines, U373MG and U87MG, IDE decreased the viable cell number and enhanced the cytotoxic effects of two known anti-proliferative agents: temozolomide and oxaliplatin. IDE also affected the clonogenic and migratory capacity of both GB cell lines, at 25 and 50 µM, a concentration equivalent to that transiently reached in plasma after oral intake that is deemed safe for humans. p21 protein expression was decreased in both cell lines, indicating that IDE likely exerts its effects through cell cycle dysregulation, and this was confirmed in U373MG cells only by flow cytometric cell cycle analysis which showed S-phase arrest. Caspase-3 protein expression was also significantly decreased in U373MG cells indicating IDE-induced apoptosis that was confirmed by flow cytometric Annexin V/propidium iodide staining. No major decrease in caspase-3 expression was observed in U87MG cells nor apoptosis as observed by flow cytometry analysis. Overall, the present study demonstrates that IDE has potential as an anti-proliferative agent for GB by interfering with several features of glioma pathogenesis such as proliferation and migration, and hence might be a drug that could be repurposed for aiding cancer treatments. Furthermore, the synergistic combinations of IDE with other agents aimed at different pathways involved in this type of cancer are promising.

Saturday, 23 February 2019

What to do in case of recurrence?

I would appreciate your helpful insights for a friend I am assisting regarding what is thought to be the best treatment options in case of recurrence? What are the most promising clinical trials? Would it be better to consider compassionate use of drugs in late-stage trials? I realize everyone's situation is different, so here are a few details:

Full resection in Aug 2018 at age 48. GBM unmethylated, IDIH wild type. Full genetic testing done, which showed he may be sensitized to a PARP inhibitor due to being BRCA1 positive, perhaps niraparib. We read that SLFN11 expression can further indicate sensitization to PARP inhibitors and his SLFN11 expression is “normal” and there are no mutations – so if this gene is important in the response to PARP inhibitors, that should be positive.  However, NO and MO say there is not enough data to show dosages of the PARP inhibitor with TMZ so are holding off on using at this time as he has just completed third round of 5/23 TMZ. They believe BRCA1 sensitizes patients to TMZ even if unmethylated. 

Is consideration for a clinical trial a better option in case of recurrence? There was something suspicious on the last MRI in a new area of the brain, so they have moved up scans to check again. He is consulting with UCSF after each scan along with local doctors. 

His cocktail also includes Valcyte, Celebrex, Metformin, Mebednazole, Keppra, Atorvastatin, Doxycycline, Bosweillic acid, Omega 3, mushrooms, Vit D, Curcumin, Probiotic, Selenium, Magnesium, Green tea extract, Melatonin, Astragalus, Milk Thistle, Lysine, Cimetidine, MCT oil, keto diet, lots of exercise. He is also on Optune.

Thank you so much for your input!

Friday, 22 February 2019

CCNU + TMZ (CeTeG / NOA-09, phase 3 trial), full article

Finally, the full article is published (not only abstract):

Lomustine-temozolomide combination therapy versus standard temozolomide therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter (CeTeG/NOA-09): a randomised, open-label, phase 3 trial.



"Between June 17, 2011, and April 8, 2014, 141 patients were randomly assigned to the treatment groups; 129 patients (63 in the temozolomide and 66 in the lomustine-temozolomide group) constituted the modified intention-to-treat population. Median overall survival was improved from 31·4 months (95% CI 27·7-47·1) with temozolomide to 48·1 months (32·6 months-not assessable) with lomustine-temozolomide (hazard ratio [HR] 0·60, 95% CI 0·35-1·03; p=0·0492 for log-rank analysis). A significant overall survival difference between groups was also found in a secondary analysis of the intention-to-treat population (n=141, HR 0·60, 95% CI 0·35-1·03; p=0·0432 for log-rank analysis). Adverse events of grade 3 or higher were observed in 32 (51%) of 63 patients in the temozolomide group and 39 (59%) of 66 patients in the lomustine-temozolomide group. There were no treatment-related deaths."

Thursday, 21 February 2019

study on the usage of Metformin

Hi everyone,

I just found this survey that says there were no significant relation between metfomin and OS or PFS of glioblastoma patients, unlike those with grade III.

http://sci-hub.tw/10.1002/ijc.31783

What do you think? Is there still any hope that they might not consider some aspect, dosage, etc that could challenge their data? I mean, is it still logical to include it in the cocktail? 

Wednesday, 20 February 2019

To do or not to do more than 6 lomustine + temozolomide cycles?

Hi folks,

My mother is a grade 4 brain cancer patient(GBM - Methylated) who was diagnosed in Sep 2017. She had a complete resection in her surgery. As of now, she has had radiotherapy + temozolomide, 3 consequent cycles of temozolomide and 6 more cycles of temozolomide+Lomustine. We switched to lomustine + temozolomide protocol because stumbled upon a reserarch at the University of Bonn because we noticed significantly improved survival rates with this protocol for methylated cancers.

http://btcocktails.blogspot.com/2017/11/sno-summary-episode-1-ceteg-trial-ccnu.html
(Median Overall survival of 46.9 months in the TMZ+Lomustine arm vs 30.4 months in the TMZ arm)

Since we started this protocol midway, we didn't go very high on the lomustine+temozolomide dosage, and wanted to complete 6 cycles. (100 mg/m2 for lomustine + 110 mg/m2 of Temozolomide for all the cycles)

My questions

Since my mom's last 3 MRIs have shown no growth, my oncologist is keen on doing 3 more cycles of Lomustine + TMZ. He has no logic/grounds backing it.

Her platelets and RBCs have always stayed stable, but her white blood counts stay between 1500-2500, and that too with iron/folic acid/filgrastim support.

Since my mom has already had more chemotherapy than most other patients and than the research that I shared, I'm not very keen on doing more of chemotherapy since it might end up having more side effects.

1. Does anyone have experience with doing more than 6 cycles of temozolomide + lomustine? If yes, how has your experience been like with going beyond the 6 cycle mark? I'm scared of her blood counts getting messed, or long term effects of going beyond the 6 cycle mark.

2. Is there some other chemotherapy protocol that you would suggest/your oncologist has suggested to keep the cancer at bay? Because the chemotherapy protocol seems to be working for my mom, and I'm very scared that stopping this might just result in the cancer coming back too.

Look forward to your response!

Monday, 18 February 2019

Optune scalp sores


I am finally having some success treating my sores. After having initial success with Clobetasol, and skin-prep, I found their effectiveness declining over the last year- bringing my compliance down from around 88% to near 78%.

I decided to try the oral route. For the last 10 days I have been taking one 24-hour Allegra. This has allowed me increase my complianceback toaround 85%.

Has anyone had similar success using an oral medication (anti-histamine,etc) or does anyone know of a stronger (prescription ?) form of anti-histamine?

Thanks,
Mike B

Friday, 15 February 2019

GBM recurrence

Dear All,

I request your opinion and advice, since our situation is very difficult. A young adult (19 years old) was diagnosed with the GBM WHO IV (gliosarcoma), and further genetic screening revealed the H3F3A G34 mutation, with ATRX, TP53, PDGFRA and others. The treatment was more or less standard Stupp protocol, with adjuvant TMZ+CCNU (as  in CeTeG trial) after the chemoradiation. After 8 months from diagnosis and the fourth chemo cycle, a diffused regions appeared in MRI scans, which our oncologists interpreted as progression, and in spite of three independent NO opinions from US, Spain and Poland, they decided to switch the chemo to Topotecan+dacarbazine (DICT). That worked for 8 cycles. During that time we tried to enroll in  a few clinical trials but without any success, usually due to the geometry and character of changes, a lack of free places, non-recruiting or closed trials and other circumstances.

Our supplements coctail was rather conservative (PSK, fish oil, melatonin, boswellia, curcumin, berberine, bee products, pterostilbene, ecchinacea, syllimarin) + anti-seizure drugs.

Unfortunately, the last MRI scan made a few days ago shows that the tumor has invaded many parts of the brain, though the primary site is essentially clean. This is a real shock for us, since the previous scan made at the beginning of December, 2018 revealed stabilization and even some improvement when compared with previous scans made on 2-months basis.

Our doctors stand at the opinion that nothing more can be done, and they sent us home (to palliative care).  I feel devastated, they give us at most a few weeks.


- Could be a metronomic TMZ (40-50mg/m^2) beneficial in this situation, as the primary tumor was non-IDH1 and likely non-MGMT, that would be the only thing to do, given that the patient has mood changes, lacks of concentration; or any other salvage chemo, Avastin, Nivolumab?

- Do you know or could you recommend a hospital/center in Europe which could provide a second and reliable opinion (like https://www.ucsfhealth.org/secondopinion/)?
 


Stefan Sobieski

Amazing G47 Delta (Herpes Virus) data from Japan for rGBM

Dear all,

Just came across a very promising phase II trial interim update from Japan, from Daiichi Sankyo's ongoing G47 Delta trial. It looks like this virotherapy is heading for fast-approval in Japan, after achieving amazing interim results in recurrent GBM:

- 1 yr survival was 92.3% (12/13 patients), vs. around 15% in historical comparisons
- Median PFS (16 people) was 8.6 months; Median OS has not been reached yet (but at least 4 with a 2 year follow-up so far)

While a small population, the results were so strong that the company is seeking to bypass the phase III trial altogether and apply in the near future for manufacturing & marketing of the treatment. Expectation would be to reach conclusion of this process within this year. It would be the first virotherapy treatment on the market.

I did not find anything on it in the English web, but here is the Japanese press release (best us web translate, which works reasonably well):

https://www.amed.go.jp/news/release_20190213.html?fbclid=IwAR3rLbU6z4MYkAoqr9trLuXQNMwKG9eLYRJd7v8YJiK-Urfex3on7zGtRtE

Very good news I believe! Hopefully we can get similar good news this year also from TOCA & DcVax. I really feel like 2019 will finally be a game changer for GBM, finally!

Best,
John

P.S. Does anyone have a view how likely it would be to get this treatment approved outside of Japan given these results?


Wednesday, 13 February 2019

Leacadinum

I'm posting this on behalf of a correspondent.

Hello!
We are  searching for medicine against brain tumor.
We found an information about Leacadinum and spoke with its creator Ivars Kalviņš. He is from Lithuania.
It was very effective instrument till 1990’. https://m.lv.sputniknews.ru/Latvia/20170220/3960096/mildronat-latvija-uchenye.html?mobile_return=no (russian articles). https://meduza.io/feature/2016/03/09/etot-preparat-spas-tysyachi-zhizney “after a course of Leacadinum use, the tumor was reduced by approximately 35–40%, metastases to the brain stem disappeared.”

And also we know story of 1 woman with GBM who survived after its using for many years (when is was in production).
Now this medicine is not producing (because of politics or something. It was bad times for USSR and its friendly countries).
We know the owner of the patent. And may be it is possible to order a test batch from him.
In this case we are searching for any information about Leacadinum:
  1. patients true stories
  2. Doctors evidences (doctors should be people after 50-60 years old I  think)
  3. May be someone of you will join us in ordering of test batch (more people=cheaper cost).
And any comments and discussions  will be helpful! 

Especially people from Lithuania are welcome! 

Neo-adjuvant (before surgery) pembrolizumab

Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma

http://sci-hub.tw/https://www.nature.com/articles/s41591-018-0337-7



This was a small, randomized trial for recurrent GBM at first or second relapse, who were candidates for surgical debulking and were on steroid doses less than 4 mg per day of dexamethasone or equivalent.  There were 16 patients in each arm. One arm (neoadjuvant) received pembrolizumab (Keytruda) 14 days before surgery, and further doses of pembrolizumab after recovery from surgery. The second arm (adjuvant) received pembrolizumab only after surgery.

The survival advantage of neoadjuvant pembrolizumab was statistically significant (hazard ratio = 0.39, P = 0.04).  Note that it's more difficult to achieve statistical significance in a smaller trial versus a larger one.  Patients in each arm were well-matched for typical prognostic features.

In light of the positive results of this trial, "we intend to expand the current study and pursue further clinical trials with neoadjuvant combination immunotherapeutics."

Tuesday, 12 February 2019

Tumor Monorail

Is there any mention on this site about this Tumor Monorail?  What are your thoughts Stephen?
https://medicalxpress.com/news/2019-02-breakthrough-device-llures-aggressive-brain.html

My husband had a focal seizure at the airport and this week had one while waiting for his f/u MRI at home.  He's never had seizures b4 this.    After 5 yrs tumor free from original GBM diagnosis,  recurrence/surgery one year ago, they now think he could have two tumors!   Time to head south to UCSF for Dr. Berger to weigh in since one tumor site looks close to the ventricle.  :-((  

Also, he's had skin cancer on his head w/2 Moh's surgeries with grafts this last summer and the rashes from that, in itself, could inhibit him having surgery, fearing if any infection could get in his brain if they open him up.     Talk about getting slammed!!!  We are waiting to hear from UCSF for their opinion.  I don't have a good feeling this round.

Candy

19 yr old with GBM, any advice for next step warmly welcomed x

Hello everyone, I've learned so much from this site already but now I have some more detailed information I'm wondering if anyone can help me with some specific advice (I apologise for the long post now)

My 19 year old daughter was in her first tern at Uni when she was diagnosed with Glioblastoma Multiforme in October, She had a craniotomy early November and most of the biggest tumour was removed. She then had the standard 6 weeks of radiotherapy (18 full brain, 12 targeted) with Temozolomide. She's had a month off and just had her first double dose 5/23 chemo (and she's been horribly sick with it and has zero appetite)

We were hoping to go down the DCVax route but it looks as though there might not be enough frozen tumour material to make a full vaccine (and we're gutted)
We had an Oncologica biomarker report and it looks like her mutations are ATM, TSC1 and TP53, her PD-L1 tumour proportion score is 90-95%, PD-L1 positive ICs 1% of tumour area (which I'm told suggests she'd be a good candidate for immunotherapy)

In terms of what Laura's currently taking, she's takes FECO 3 times a day, Keppra, Chloroquine and she's also on the Care Oncology protocol (Metformin, Atorvastatin and Vermox)

Supplement wise she also takes;
Boswellia
Berberine
Bromelain
Longvidia Curcumin
Milk thistle
Melatonin
Artemisia
Vitamin A D K
Resveratrol
Grapeseed

So the reason for the post is to ask if any of you wise people have any suggestions as to where we could look next? I think we might struggle with dendritic cell therapy due to the small sample size but is it possible to get hold of immunotherapy drugs or is that only an option if you're on a trial?

Laura was just getting started in her life and I'll do whatever I can to give her the best possible change of a happy life.
Thanks very much for reading and best wishes to you all
Nicola x


Hi to everybody. My 69-year-old mother was diagnosed with glioblastoma in december 2018. We realized that she was missing a few words in reading, writing and talking and having constantly headache. It was operated on 12/27/18, when approximately 90% of a tumor was removed. She never had any seizures. After the surgery she had a considerable improvement in writing and reading and did not fell any more headaches, despite having presented a little tremor in her hands. Radiation therapy started on 01/23/1919 and was fractionated in 15 sessions. The first cycle (21 days) of temodal (temozolamide - TMZ) chemotherapy was started on 05/02/19.

Since the surgery she has been taking:

- Omeprazole
- Pure (she has hypothyroidism)
-Paroxetine
- Depakene 500 mg twice a day
-dexametazone just one per day
zolpidem

and supplements:
- magnesium chloride
-D vitamin 10,000 cu
- curcurum (curcumin)
-Omega 3
metatonin (15) at night

started recently:
resveratrol
1 clove garlic, raw

and will start:
-Beta Glucan
-artemisinine
-genysteine
sibyllin


We are thinking of associating acetatalozamide with the next cycles of temozolomide.

I would like you, or someone, to evaluate, and please and if possible make some comments and suggestions.

Note: We have not taken the MGMT exam yet.

thanks in advance

Thursday, 7 February 2019

Request for choosing a suitable cocktail



Hi everybody and many thanks to Stephen for adding me to
this wonderful blog.
I have some questions regarding my father situation and it’s
a bit embarrassing cause we don’t have detailed information about the tumor as
many of you have, so I wonder if someone could kindly help me to choose the
best probable cocktail for him while I know that it is just a shot in the dark.

He is 69 years old and last year (March 2018) during working
with probably toxic glue he suddenly fainted out and later he had problem in
his stomach. We went through lots of colonoscopy and other procedures during a
year and he lost more than 10 kg. Finally (at September 2018) we had a MRI that
said low grade glioma (in the LT temporal)
is the first possibility. (I guess since his HDL and LDL cholesterol were 41
and 77 mg/dl in July 2018 the tumor was not aggressive at that time). We’d been
told that because of tumor location it is better to do nothing and just wait.
(I am suspicious about
Finasteride pill that he took for 3 years for his prostate and we recently switched
to Terazosin)
Then in December we had
the second MRI which shows a “51*47*24 mm heterogeneous mass with surrounding edema
and extension to hippocampus region and mass effect on the LT with mild mid
line shift”.
Then we went through a
painful process to decide whether we should take the risk of surgery and
finally we decided not to (which I am still doubtful about it). After a stereotactic
biopsy which only says this:
  •  Microscopy:




Sections reveal fragments
of tissue including an astrocytic neoplasm. The cellularity is high. The cytologic
atypia include unclear hyperchromatism and some pleomorphism with scattered
cells having larger more hyperchromatic nuclie, occasional multinucleated. There
is rather extensive necrosis with prominent vascular and endothelial
proliferation.
  • Diagnosis:







Astrocytoma, anaplastic
with necrosis (glioblastoma multiforme), left temporal and basal ganglia involvement.
 



We started the temodal (120)+ radiotherapy (30 sessions) recently and now he
is in his second week.
He is taking 1 sodium
valproate 500, had around 25 dexamethasone (finished now), 3 phenytoin 100, 2 ranitidine!,
and 1 Terazosin a day.

I am trying to persuade
his Drs: to change ranitidine to cimetidine and maybe adding metformin (since he
had lost many weight I don’t know if they accept this and as someone mentioned
here metformin and cimetidine does not go well together. Am I right? But cutting
his carbohydrate too much is quiet hard so I still like metformin)

Also maybe chloroquine if
they accept.

-        
So the first silly question is that, if he goes well with the first cycle
can we say his tumor is methylated?
-        
Do you think Turmeric curcumin NovaSol could work as a replacement for
Longvida? Because of his weak stomach I thought soft gels might work better.  (https://www.amazon.com/Turmeric-Curcumin-NovaSOL-Bioperine
Softgels/dp/B018GQJQHM/ref=sr_1_2_s_it?s=hpc&ie=UTF8&qid=1533759320&sr=1-2&keywords=NovaSol%C2%AE&dpID=61EqNrydTdL&preST=_SX300_QL70_&dpSrc=srch
)

-        
What would you suggest for such a vague situation for a cocktail or other
therapy? (
  Ttf and vaccine are not available here)


I know most of information I said are useless but I thought it might help for some better guess. 

Many thanks in advance,

Sahel


Tuesday, 5 February 2019

Chemoradiation + PCV + Cannabidiol for IDH1-mut secondary GBM

Case Report: Clinical Outcome and Image Response of Two Patients With Secondary High-Grade Glioma Treated With Chemoradiation, PCV, and Cannabidiol
Dall'Stella et al. 2019

link to full study

Monday, 4 February 2019

Drugs to Combine with CCNU

My husband will soon begin CCNU for recurrence. In reviewing Ben Williams' document, I see that Verapamil and Calcium Channel Blockers like nimodipine have some evidence for augmentation benefit; however, the articles I found (both from his references and my own search) are quite old. Verapamil has more drug interactions than nimodipine. Is there any research about these drugs or other potential augmenters which I might share with his NO? (His NO has generally been supportive of repurposed drugs when I can share relevant studies. His NO does not want to combine CCNU with TMZ despite CeGaT study due to increased toxicity.)

Much gratitude and well wishes to all--
S.

Saturday, 26 January 2019

Advice for a 8 year-old boy with diffuse midline glioma, BRAFV600E and H3K27M mutation

Dear Stephen, dear all,

Anatole, my 8 year-old son has been diagnosed in May 2018 with a diffuse midline glioma on the right thalamus. We are French and based in Stockholm, Sweden. We followed the proposed protocol with the local medical team who works in partnership with Gustave Roussy institute in France but we want to go further now, and we need your advice. The local medical team is not very aware of alternative medication but is willing to help.

Molecular status of the tumour:
BRAFV600E and H3K27M mutation
NF1 and MLH1 mutation
We have little chance to find new targetable alterations by a deeper sequencing. It is possible now that the V600E BRAF mutation is lost in the resistant cells but anyway we do not think it is wise to treat with a V600E BRAF inhibitor which in our experience could speed up tumor growth.  

History:
18/05/09 Diagnosis: MRI tumour size 3.3x3.7x3.7cm, unusual calcification
18/05/16 Biopsy, leading to light hemiparesis
Proton-therapy 18/07/02-18/08/13, 1.8Gy x 30 = 54Gy. Almost fully recovered from hemiparesis
18/09/07 Headaches
18/09/07 MRI tumour size about 4cm
18/09/12 Ventriculostomy
18/09/19 Beginning og Dasatinib (100+70mg/day), after 18/11/06 alternating with Everolimus (5mg/day) every 2 weeks (Biomede protocol)
18/09/22 Beginning of hemiparesis
18/10/03 Wheelchair for walks more than 20m
18/10/12 MRI tumour size 5 to 6cm unsure if pseudoprogession
18/10/22 Beginning of Bevacizumab then once every 2 weeks
18/11/06 Beginning of Everolimus  
18/12/03 MRI tumour size 4 to 5cm unsure if pseudoprogession
18/12/17 Crook for walks less than 20m
19/01/14 MRI tumour size 5x6x5cm
19/01/22 Stop all current chemo (Dasatinib and Everolimus, last Bevacizumab 19/01/02)
24/01/24 PET scan (methyonine)
New plan established by Gustave Roussy Institute: Mebendazol, investigation for debulking of calcification before re-irradiation, eventually ONC201
Any comment on this plan?

Supplements:
Anatole is 30kg 132cm  
D3 vitamin since 18/12/24: escalading from 40µg/d to 100µg/d now
Fish oil since 18/12/24: 1g
Melatonin since 19/01/10: escalading from 2mg/d to 5mg/d now
Turkey tail since 19/01/25: 500mg/d

We plan to add soon:
Longvida Curcumin: 800mg/d
Milk thistle: which dose would you recommend? 
Green tea extract: which dose would you recommend? 
Broccoli sprouts: which dose would you recommend? 
Metformin: Is it worth considering for a child?

Anything else you would find suitable considering his condition (celebrex, chloroquine, clomipramine, berberine, selenium, probiotics, etc?

Diet:
We follow a light low carb diet now (no refined sugar or flour, very limited sugar, no processed food, only bio food). We are planning to begin a ketogenic diet soon, we are ready to change all our habits. We will contact a dietetician specialist in this diet. Anybody else with an experience of ketogenic diet with children?

Thanks to all of you for your precious help, any contribution could help.
Fabrice

Sunday, 20 January 2019

Cannabis oil treatment (THC)

Dear Stephen, dear all!

What do you think about using cannabis oil with a high content of THC component to treat glioblastoma. (Exact component concentration is not known (but declared as high).

Based on recommendations of one doctor, the oil should be applied according to the following scheme (it's also known as Rick Simpson's scheme):
* first day - one drop x 2 times a day;
* then every three days increase intake by one drop in the morning and evening
* reach 24 drops (approximately 1 ml) and take this amount x 2 times a day.

There are a lot of wonderful stories about its anti-cancer effect in the Internet, especially in case of brain tumor. But then I found this research http://cancerres.aacrjournals.org/content/64/6/1943.long#sec-10.

"Treatment of the glioblastoma cell line U373-MG and the lung carcinoma cell line NCI-H292 with nanomolar concentrations of THC led to accelerated cell proliferation that was completely dependent on metalloprotease and epidermal growth factor receptor (EGFR) activity."

"In the light of these results, the use of cannabinoids in cancer therapy has to be reconsidered, because relatively high concentrations of THC induce apoptosis in cancer cells, whereas nanomolar concentrations enhance tumor cell proliferation and may, therefore, accelerate cancer progression in patients."

"Smoking of THC is the most effective route of delivery, as THC is rapidly absorbed after inhalation, and the effects become fully apparent within minutes. Pharmacological activity of smoked THC depends on the depth and length of inhalation. Maximum serum concentrations up to 267 ng/ml (850 nm) are measured after smoking THC, whereas maximum serum concentrations of oral or rectal administered THC or its derivatives as a drug are lower (35–350 nm). Here we observed a proliferative response of glioblastoma and lung cancer cells at concentrations of 100–300 nm THC, whereas THC at micromolar concentrations induced cell death in agreement with previous observations with neuronal cell types and immune cells. These findings indicate that the biological responses to cannabinoids critically depend on drug concentration and cellular context. Taken together, these results have to be taken into account when considering therapeutic applications of cannabinoids. The risk in the medical use of THC or cannabis for the treatment of patients with established tumors is the further acceleration of tumor growth due to the proliferative potential of cannabinoids."
Questions:

1. Has anyone tried to measure THC concentrationt in the blood? Are there any tests for home use that can show the quantitative content of this component in the blood? I know that there are tests for saliva and urine, but how to compare blood concentration and saliva/urine?

2. Perhaps it is easier to measure the THC concentration in one oil drop? And then to estimate what concentration it causes in the blood?

3. Do I understand correctly that THC has a cumulative effect when using daily and in principle it is real to achieve micromolar concentration after some time?

4. Is it possible to avoid the psychotropic effect with micromolar concentration?

5. Is THC effective by itself or only with radiation therapy or chemotherapy?

6. May be it's really better smoking if it allows to achieve more THC concentration? 

I am looking forward to your answers! Thank you!


And please accept my late congratulations with New Year! Let it be full of wonders! Health to all of you and your loved ones!

Irina

Recurrant anaplastic astrocytoma treatment options

Hey all,
Need suggestions for treatment options and supplementation for my brother
His clinical history is-
clinical history date remarks
diagnosed in                                                                                                         september 2009                               assumed to be begnin tumour
                                                      observation through mri 
Tumour surgical resection 18th feb 2016 tumour started to enhance in size
gross resection of more than 95% 
tumour size 7.2x5.5x5.1( anaplastic oligoastrocytoma)
RT PLUS  CONCURRENT TEMOZOLOMIDE 2ndAPRIL 2016 TO 17th MAY 2016 59.4 gy ,33 fractions plus 120 mg temozolomide
Temozolomide june 2016 -december 2016 6 cycles
Recurrence                                                  may-18         
reradiation +concurrant temozolomide 18th jul 18-16th aug 18 36gy, 20 fractions plus 120 mg temozolomide
temozolomide chemo 1st jan 19-5thjan 19 200mg per day for 5 days                              
HIS BIOMARKERS ARE-

BIOMARKER AND GENOMIC FINDING STATUS
MICROSATELLITE STATUS MS-STABLE
TUMOUR MUTATIONAL BURDEN  TMB-LOW (4 MUTS/MB)
ATRX  LOSS
IDH1 R132H
NOTCH1 A465T SUBCLONAL,E450K-SUBCLONAL,R353C-SUBCLONAL
SMARCA4 T910M
TP53 G245S,R273C
MGMT UNMETHYLATED(METHYLATION SCORE-0.49)
ANTIBODY TYPE RESULT
GFAP POSITIVE
IDH1 R132 POSITIVE
KI-67 POSITIVE PROLIFERATIVE INDEX APPROX 10-15%
FISH TEST
1P/19Q CO-DELETION NEGITIVE
EGFR NEGITIVE FOR EGFR AMPLIFICATION
PTEN LOSS POSITIVE (39.3% OF NUCLEI EXAMINED)
His current medications are-

Part of Day Medicine Name Medicine count Notes
PRE MORNING BROMELAIN 500 MG NOW 3 EMPTY STOMACH
TAB PAN 40 MG RT OD 1 STOP ON 30TH JAN 2019
MORNING BREAKFAST CURCUMIN TABLETS 3 NOT WITH AVASTIN OR TAGRISSO/TARCEVA
GLYCEROL 30 ML 1
DIAMOX 250 MG 1
METAFORMIN 500MG 1 TWICE DAILY FROM 1ST FEB
IBUPROFEN 200 MG 1
CBD OIL 2 FULL DROPPERS 1
LEVIPILL 750 MG RT 1
LASILACTONE 20/50 MG RT 1
TAB DEXA 4 MG RT 1 STOP AFTER 21ST JAN
TAB BACLOFEN 5MG RT 1
REFRESH EYE DROP 2 BOTH EYES 2 DROPS
LEVOLIN NEBULISATION .63MG 1 STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 20TH JAN
TO BE ADDED VALGANCICLOVIR 450 MG 2
CHLOROQUINE 250 MG 1
CELEBRAX 200MG 1
WHEY PROTIEN 2 SCOOPS  WHEN RECD FROM USA
GRAPESEED EXTRACT 250 MG 1
STRESS B COMPLEX 2
LUNCH CURCUMIN TABLETS 3
MEBENDAZOLE 100 MG 1 START DOXYCYCLINE ON 18 TH APRIL
GLYCEROL 30 ML 1
IBUPROFEN 200 MG 1
LASIX 40 MG 1
REFRESH EYE DROP 2 DROPS STOP AFTER 21ST JAN
LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN
TO BE ADDED CELEBRAX 200MG 1
NIGHT CURCUMIN TABLETS 3
ATORVASTATIN 40 MG 1 80 MG FROM 1ST FEB
GLYCEROL 30 ML 1
DIAMOX 250 MG 1
IBUPROFEN 200 MG 1
CBD OIL 2 FULL DROPPERS 1 AFTER HALF HOUR GIVE THC 6 DROPS
THC OIL 6 DROPS 1
LEVIPILL 750 MG 1
LASILACTONE 20/50 MG 1
TAB BACLOFEN 5MG RT 1
REFRESH EYE DROP 1 BOTH EYES
LEVOLIN NEBULISATION .63MG 1 TIME STOP ON 25TH JAN 2019
TAB GLYCOPYRROLATE 1 MG 1 STOP ON 2O TH JAN
TO BE ADDED VALGANCICLOVIR 450 MG 2 STOP ON 9TH FEB 2019
CELEBRAX 200 MG 1
BERBERINE 500 MG 1
BEDTIME ARTEMISIA 500 MG 2 WHEN RECD FROM PATRICE
TAB FRISIUM 5MG RT 1
PLEASE SUGGEST
1.SUPPLEMENTS TO ADD OR TO BE DISCONTINUED
2.AVASTIN OR LOUMUSTINE OR ANY OTHER TRIAL DRUG BEST SUITED FOR HIM
3.ANY OTHER EFFECTIVE THERAPY TO HELP HIS QUALITY OF LIFE.