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

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?

Repurposing of idebenone as a potential anti-cancer agent.


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.

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.
(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?

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

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):

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!


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


I'm posting this on behalf of a correspondent.

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’. (russian articles). “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

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?

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.


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;
Longvidia Curcumin
Milk thistle
Vitamin A D K

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)
- Depakene 500 mg twice a day
-dexametazone just one per day

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

started recently:
1 clove garlic, raw

and will start:
-Beta Glucan

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
  • 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.  (

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,


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--