Results of Ivosidenib (inhibitor of mutant IDH1) for nonenhancing IDH1 mutant gliomas

Just published in the Journal of Clinical Oncology

Ivosidenib in Isocitrate Dehydrogenase 1–Mutated Advanced Glioma
https://sci-hub.tw/10.1200/JCO.19.03327

• out of 35 patients with nonenhancing glioma, objective response rate was 2.9% with one partial response
• of these same patients, 30/35 (85.7%) had stabilization of their disease.
• for these same 35 patients, median progression-free survival was 13.6 months.
• the drug was well-tolerated with no dose-limiting toxicities reported.

As seen here, many of the patients with non-enhancing glioma have had disease stabilization for three years or more.  Not bad for a drug that is so well tolerated and with no dose-limited toxicities.

Lomustine questions

Hi all

I'm posting on behalf of my sister with some questions about her treatment plan.

First, some background history:

2009: Initial diagnosis with full resection and biopsy diagnosed with grade 2 astrocytoma, resulting in watch and wait approach with no radiation / chemo and regular MRIs

2019: 10 yr MRI scan revealed recurrence of tumor in same location; partial resection and biopsy showed very localized portion of tumor had increased proliferation index resulting in grade 3 astrocytoma finding. She completed the IMRT and temodar (TMZ) regimen and has been on TMZ since last summer. She's being treated at Duke's Preston center.

She is IDH1 positive and no 1p/19q co-deletion

Due to COVID-19, her March scan was not conducted by Duke but rather by a local rural center and the scan showed evidence of progression in one area. She has a follow up scan next week at Duke.

Duke is recommending she 1) switch to lumostine (CCNU) or 2) enroll in the STELLAR trial in hopes to be randomized to the CCNU+eflornithine arm. 

Questions for the group:

1) If she gets randomized to the lomustine alone arm, is there any real clinical or prognostic value to in staying in the STELLAR trial given that her non-trial treatment option is lumostine anyway and she would have fewer restrictions not in the trial

2) I am recommending she also take papaya leaf extract given the suggestion that it can help with platelet counts which is a known side effect of lumostine. Duke did not want her to take it because it has "antioxidant properties" which doesn't make sense. Does anyone understand this concern?

Thanks for the feedback and the resource of this group!!

CBD + ALA combination (GBM)

Hi

Do you have any thoughts on combining CBD with alpha-lipoic acid (ALA)? I haven't found any specific research on a combination. I am particularly interested in IDH-wild



Also... I would like to link some interesting stuff :

Concomitant Treatment of Malignant Brain Tumours With CBD - A Case Series and Review of the Literature
https://pubmed.ncbi.nlm.nih.gov/31570484/
"a total of nine consecutive patients with brain tumours are described as case series; all patients received CBD in a daily dose of 400 mg concomitantly to the standard therapeutic procedure of maximal resection followed by radiochemotherapy. By the time of the submission of this article, all but one patient are still alive with a mean survival time of 22.3 months (range=7-47 months)".

Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures
https://www.nature.com/articles/s41598-020-59468-4
(CBD + chloroquine + radiation)

RelA-activity is essential for Cannabidiol-mediated cytotoxicity
https://academic.oup.com/neuro-oncology/article-abstract/21/Supplement_6/vi70/5619524?redirectedFrom=fulltext (no full research report available)
"We observed therapeutic efficiency of CBD in a subset of GBM, obtained genetic markers indicating CBD-sensitive GBM and found that the p53 status segregated cell-death modes".

Additionally - if somebody is considering CBD, CBG, or FECO, there is a new report you might be interested in (sadly, no real specifics, that's commercial research):
https://thegreenfund.com/mcg-pharma-cannabinoid-formula-to-treat-glioblastoma

Mebendazole, recommended phase 2 dose in high grade glioma

https://www.ncbi.nlm.nih.gov/pubmed/32400117
Reverse swing-M, phase 1 study of repurposing mebendazole in recurrent high-grade glioma.

"Interpretation: The recommended phase 2 dose of mebendazole is 1600 mg TDS with temozolomide and temozolomide-radiation combination while the dose of 800 mg TDS needs to be used with single-agent CCNU."

TDS apparently means three times daily, so 1600 mg TDS = 4800 mg per day total.

Deciding between Chemo and Targeted Therapies for Recurrence

I've been a longtime follower of this community and I'm hoping that others here can help me cut through all the information I'm being given to make some decisions for my husband.

Background
My husband was diagnosed at age 34 in October 2018 after having neck pain for a few weeks and then a sudden onset of extreme disorientation. He had an emergency resection (97.8% debulked). His tumor was originally located in the left parietal lobe. His tumor is unmethylated, IDH wild-type. Initially he followed SOC. Radiation concurrent with TMZ, then Stupp protocol 5/23 with Optune.

In May 2019, he had progression, stopped TMZ and Optune in preparation for surgery. Second resection in June 2019. He got a pre-surgical infusion of Keytruda (Pembrolizumab). Second surgery was MRI assisted at Memorial Sloan Kettering. Resection was successful and he followed with a short course of photon radiation and Keytruda infusions every 3 weeks. Around this time we also stopped doing a strict Keto diet because he had dropped close to 40 pounds. We now follow it in moderation.

We used Store My Tumor to preserve a tissue sample from the second surgery and used that to create an autologous dendritic cell vaccine from whole tumor lysate at Thomas Nesselhut's clinic in Germany. He was primed with an oncolytic virus, also used adjuvants of Inter-leukin 2 and Aldara cream.

Fall 2019 we continued Keytruda infusions and his dendritic cell vaccine with Tetanus adjuvant. In October 2019 he had an adverse event (possible focal seizure or pressure wave). We discontinued Keytruda (had completed 7 rounds). Started on a course of Avastin infusions and 4 mg Dexamethasone to control inflammation. We made the decision to discontinue Optune at this time. It was a quality of life decision. It was really interfering with his enjoyment and activity (we have twin toddlers). I am 100% okay with that decision and won't force him to do something he hates.

In November 2019 he was accepted into the SurVaxM clinical trial via compassionate release. He completed a priming dose (4 rounds) of the peptide vaccine SurVaxM. His most recent dose was in April 2020. In January 2019, it looked like there was further progression in the corpus callosum. We decided to continue with Avastin infusions and dendritic cell treatment and did a course of Proton Beam radiation.
His first MRI post radiation showed a modest reduction in tumor. (March 2020).
His most recent MRI in May 2020 is showing new growth. The area that got proton beam radiation continues to shrink, but there is a new tumor measuring 2.9 X 1.7 cm within the posterior medial left temporal lobe. Thankfully he has remained largely asymptomatic and stable. He has issues with leg weakness from prolonged steroid usage and his right arm and hand have lost dexterity. He has never had a seizure. He has some memory issues and lately some issues with processing.
Now we are faced with a decision about what to do next and we are getting a lot of differing opinions.
His tumor has the following markers:

x





We are deciding between adding a cytotoxic chemotherapy and a targeted therapy. One team of doctors is strongly recommending CCNU. Their other options would be Metronomic TMZ, Carboplatin, or Irinotecan.

Our vaccine team is very wary of cytotoxic chemo and believe it would negate the immunotherapies. They are okay with metronomic TMZ or metronomic Cytoxan.

A third doctor recommended Carboplatin and keeping Keytruda.

We have been offered the possibility of trying a targeted therapy to match his genetic markers. The choices there are Abemaciclib (CDK4/6 inhibitor) or Cabozantinib (MET fusion). I would like to get a PI3K/Mtor inhibitor or an MDMA inhibitor but there are next to none that are commercially available and I don't think we can get into any trials or want to wait that long. Piqray is one potential option in the PI3K/Mtor area. We don't know if we could combine them with chemo. I think we would have to see how he responds to one before adding them together.

Surgery and radiation seem unlikely though we are going to pursue consultations for surgery (we are based in NY) and gamma knife with Dr. Christopher Duma. I don't think these will pan out, but the consultations can't hurt.

I am really struggling with how to make these choices. His quality of life is fairly good. None of these options seem to have strong data behind them, but all have those small percentages of patients where things work and no one knows why.

I want to make a decision quickly. I am leaning towards Metronomic chemo (even though I know he is unmethylated and the chances of it working are small). But we can get it immediately and we know somewhat how he responds on chemo. He always tolerated it well, never had low counts and managed side effects with cannabis and IV fluids and colace. I think we could try chemo for one month and do another scan and see quickly if there is any impact.

We would have to get approval for the targeted therapies and I think perhaps it makes the most sense to hold those while we try something else.

He has been on his vaccine for almost one year and I have no idea if it has done anything, perhaps it's simply held things back.

I know this community has so much knowledge. I welcome any insight. He is 19 months past diagnosis and we have never had a long stretch of stability. We have thrown everything at this disease. Given how aggressive its been, I hope that all that we have done has given him more time than if we had just done SOC. I want to give him time, good time.

His genetic markers are:
TERT
CDKN2A
MDM2
CCND2
PTEN
FOXP1
TET2
YAP1
CCND2
BIRC3
PTPRZ1-Met Fusion

We completed EVA-PCD assay through Nagourney Cancer Institute. Tumor tissue sample allowed for testing of 5 agents. Results were:

• Dactolisib (PI3K/mTOR)--sensitive

• Palbociclib (CDK4/6)--sensitive

• Crizotinib (ALK/MET/ROS)--intermediate

• Carboplatin & Topotecan--intermediate

• Olaparib (PARP)--resistant

His medications are as follows:

Immunotherapy

Dendritic Cell Vaccine

SurVaxM vaccine

Keytruda

Tetantus adjuvant

Aldara adjuvant

Lion's Mane

Apoptosis/Autophagy 

Chloroquine 

Mebendazole 

Artemisinin 

Simvastatin 

Escozine 

Anti-Angiogenic

Avastin

EGCG 

Metabolic 

Metformin 

Anti-Inflammatory

Bromelain 

Curcumin 

Boswellia Serrata

Quercetin

Other 

Cymbalta 

Clonazepam

Valproic Acid

Melatonin

Turkey Tail

CBD (sublingual)

Cannabis (whole flower, vaporized as needed)

 

Please, help

Hello everyone. I ask you for help and advice, share personal experience. My mother is 57 years old, she was diagnosed with degree IV glioblastoma, IDH 1 mutant, methylated MGMT. She underwent complete removal of the tumor, went through 30 sessions of 2 gray. Now we need to undergo chemotherapy. TMZ or TMZ + CCNU? What other drug combinations are possible? What dietary supplements can be taken and in what doses, in what mode? I will be very grateful for any information and advice. Many thanks and health to all of you!

Major study of hypermutated gliomas published in Nature

Mechanisms and therapeutic implications of hypermutation in gliomas.
https://www.ncbi.nlm.nih.gov/pubmed/32322066
https://sci-hub.tw/10.1038/s41586-020-2209-9  (sci-hub link to the full PDF document)

Unfortunately this study provides negative evidence to the idea that hypermutated gliomas would be more responsive to treatment with PD-1 blockers such as nivolumab and pembrolizumab.

from the study
"MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade. "

"Because our prior analyses indicated that patients with hypermutated gliomas might have reduced survival, we used a second set of historical controls to compare the outcome of hypermutated gliomas treated with PD-1 blockade versus other systemic agents. Unexpectedly, we observed a longer median OS for patients treated with other systemic agents when compared to those treated with PD-1 blockade"

However, the mismatch repair deficient, hypermutated tumor cells were sensitive to the chemotherapy agent CCNU (lomustine).

"We next treated native and engineered isogenic MMR-knockout glioma models with temozolomide or the nitrosourea lomustine (CCNU), a chloroethylating alkylating agent that generates DNA interstrand crosslinks and double-strand breaks (Fig. 2c, Extended Data Fig. 8g–i). All MMR-deficient models were resistant to temozolomide and sensitive to CCNU, consistent with the lack of hypermutation in samples from nitrosourea-treated patients"


This confirms advice I've given to patients with temozolomide-driven hypermutated recurrent gliomas: CCNU (lomustine) chemotherapy is probably the best choice in terms of conventional chemotherapy options.  However it argues against advice that PD-1/PD-L1 blockade (drugs such as pembrolizumab or nivolumab) would be the best option.

Niacin reactivates myeloid cells, slows tumor growth in GBM mouse models

This was just published a few days ago in Science Translational Medicine.

Control of brain tumor growth by reactivating myeloid cells with niacin
Sarkar et al.
https://stm.sciencemag.org/content/12/537/eaay9924.editor-summary


"Although innate immune cells are typically present inside tumors, they often have an inactive phenotype such that they are ineffective at killing the cancer cells or even promote tumor growth. Sarkar et al. discovered that it may be possible to reprogram these cells to a more active type using niacin (vitamin B3). The authors showed that niacin-exposed monocytes can inhibit the growth of brain tumor–initiating cells. Moreover, niacin treatment of intracranial mouse models of glioblastoma increased monocyte and macrophage infiltration into the tumors, stimulated antitumor immune responses, and extended the animals’ survival, especially when combined with the chemotherapeutic drug temozolomide."

I have uploaded the full study to the Brain Tumor Library, follow this pathway:

Folder 0. Important Reference documents -> subfolder 1. New Uploads ->  "2020 Sarkar Niacin reactivates myeloid cells"

Unused temozolomide

from Candy:

I have 4 months worth or TMZ that has not been opened. Downside is it expired 2/2020. Not real sure that matters since recent. If anyone is in need, I will be happy to mail in US at no cost for items or mail.  
Stay safe.
Candy


from Stephen:

if there are any takers I can connect the parties by email

Posted on behalf of a caregiver:

My sister (aged 42) has glioblastoma grade IV, IDH mutated.
Previously diagnosed with an infiltrating astrocytoma (WHO grade II) in 2015 in the left inferior front temporal region, now transformed to glioblastoma.
She had 2 surgeries in 2016 to take out as much of the tumour as possible, and followed up with radio and chemo. She has been taking the following medication:

Anti-seizure

Levetiracetam – 1000mg/morning and night

Apo-clobazam – 10mg/ night

Vimpat (Lacosamide) – 10mg/morning and night

Anti-cancer 
Disulfiram – 500mg/morning 
Copper (Bisglycinate) – 10mg/morning 

Niacin (No Flush) – 500mg/morning 

Anti-"pup" medications

Metamucil fibre therapy

RestotaLax

Supplements

Boswellia – 307mg (115 mg Boswellic acids)

Turmeric / Curcumin (Anti-inflamatory) – 500mg twice daily

Mushroom Complex 2-3 pills twice daily

Vitamin D -5000IU daily

Melatonin – 10 mg

Green Tea Extract – 300mg

OMEGA 3 FATTY ACID (FISH OIL) 3000mg daily

COENZYME Q-10 -100mg once daily

Repurposed Meds for brain tumor

Metformin – 500mg X 2 tables

Mebendazole – 100mg X 2 tables

Atorvastatin – 40mg X 2 tables

Doxycycline - 100mg (alternantes monthly)

Her MRI has been coming back ok (I.e. tumour size remains d same, not increasing nor reducing), most recent MRI being in Feb.
However since late last year, she has been losing her balance and falling.

My question for this group is if anyone here has experienced something similar? I’m seeking some insight on why MRI is clean but balance is worsening. 

@Stephen, I’d appreciate if you have any comments on this.

Any help will be appreciated.

Also if you have any advice on something else we can try kindly let me know.

Many thanks 

Side effects of methadone

https://www.ncbi.nlm.nih.gov/pubmed/32060760

Safety aspects of opioid-naïve patients with high-grade glioma treated with D,L-Methadone: an observational case series.

from the abstract:

"Twenty-four patients were included. All patients were opioid-naïve and received D, L-Methadone from their general practitioners. Sixteen patients experienced side effects. The median dosage when side effects began to occur was 15.8 mg/ 24 h. Fatigue and mood changes were reported most frequently (14 of 24 patients). Five patients had severe side effects related to relatively high doses. In all cases, symptoms resolved after cessation or dose reduction. Our results show that D/L M intake lead to frequent occurrence of side effects in opioid-naïve patients especially when not handled with caution and close supervision. Patients, their relatives, their GPs and neuro-oncologists need to be informed about the broad spectrum of side effects in order to thoroughly counsel glioma patients."

New Research: High fat (keto) diet accelerates glioblastoma growth

Hi all,

Just popped up on my news feed is this paper: https://www.biorxiv.org/content/10.1101/2020.03.08.982116v2, which suggests that the high-fat 'keto' diet (which I know many people are taking in an attempt to limit tumour growth) may actually be counterproductive and speed glioblastoma growth. Here's the lay summary:

"Consumption of a high-fat diet (HFD) accelerates glioblastoma (GBM) by inhibiting the production and signaling of the tumor-suppressive metabolite hydrogen sulfide (H2S)"
**Note that this a 'pre-print' article that has not yet been certified by peer review.

I would be interested to hear people's opinions.

CBD bio-availibility

Saw an article in Neurology about the effect of high fat meals on CBD uptake.  Showed significantly more bio-availability with high fat meals.  Roughly 4x increase with high fat meal, 2x increase with low fat meal, vs a fasted state. 

Useful info for those using CBD for treatment.  Note this paper did not investigate THC which will behave differently.

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16419

Sourcing chloroquine

I have been using chloroquine phosphate (250mg od) as part of a cocktail for anaplastic astrocytoma. It is becoming increasingly difficult to source in the UK and I think most places aren't stocking it anymore (presumably because of malaria resistance). Does anyone have any advice on how I may go about sourcing more?
Any advice welcomed!

Brain Tumor Library - "New Upload" folder

I've added a new folder within the Brain Tumor Library folder which I've shared with over 500 patients and caregivers.  The new folder is called "1. New Uploads", and will be a way for frequent users of the library to see at a glance new studies that I've added, before they are filed away into their destination folder a month or so later.

Good luck in your research!

Chlorpromazine trial

Repurposing Chlorpromazine in the Treatment of Glioblastoma (RACTAC)
https://clinicaltrials.gov/ct2/show/NCT04224441

This is a phase 2 trial being conducted in Italy.

Two interesting points to remember:
Chlorpromazine is an old off-patent drug, in clinical use since the 1950s.

Like the new drug ONC201 (which is in several trials and an expanded access program for H3 K27M mutant gliomas and DIPG), it is an antagonist of dopamine receptor D2 (DRD2).

Feb 5 2020 edit:

See also
https://www.ncbi.nlm.nih.gov/pubmed/32005270
Repurposing chlorpromazine in the treatment of glioblastoma multiforme: analysis of literature and forthcoming steps.

A personal note

Some of you may have noticed a decline of activity from me on the blog, and I feel it is time I made some kind of statement about it.

It has been 7 years since my good friend was diagnosed with anaplastic astrocytoma. Prior to that time, I had not even heard the term "astrocytoma" before, neither did I have any formal training in the sciences.  The story may be familiar to some of you.

Unfortunately over the past couple years, especially over the last year, I've felt as though I'm "running out of steam" for this kind of work.  Burnout is another term that might fit.  I've never wanted to abandon this community, as I'm fully aware of how much need there is for the kind of brain tumor research inspired by people such as Ben Williams, who has been the intellectual inspiration for my work.  Yet, I have to be honest with myself and with you the community, that I'm feeling its time for a hiatus.  Rest assured, this doesn't mean I'm shutting down the blog.  If anyone feels knowledgeable enough to step up and take a more active role in answering questions posted here, that would certainly be welcome.  I will continue to monitor the activity here and may be able to contribute something, just as others do.  I feel like I can continue to be a contributor here, but probably not as the primary voice responding to the majority of posts as I was able to do in past years.

I'm not sure what this will mean in terms of continued lively discussion here.  I would also like to mention the new forum at virtualtrials.com, which has started since the closing of the previous yahoo discussion groups. I'd encourage you all to check out

https://forum.virtualtrials.org

Al Musella was a huge help to me when I was new to the brain tumor research community, and provided me with many opportunities to meet others in the field, attend conferences etc.  Let's all support his work and the new forum he is providing.

This is not goodbye, just stepping down from the more prominent role that I somehow fell into, when my energy levels for scientific research were higher than they are at present.  I wish each and every one of you the best of luck in your research,  hope you find the answers you are seeking in the archives here, and from other sources, and of course hope that you will be able to beat the prognosis given to you by the medical establishment.

Sincerely,
Stephen W

Please help evaluate the urgency of tumor relapse (gliosarcoma GIV)

Dear all,


I need your advise and support.

My sister has gliosarcoma GIV (please see our medical history here). Last MRI figured out relapse of tumor growth. How evaluate property real level of urgency and real speed of tumor growth?

Links for MRIs are here

Should we look for the option of another surgery  (rejection)? Is there any chance to do it without trepanation of skull? I heard this may be done with ultrasound. What are the best options for surgery?

Thanks in advance for your help and recommendations.

Good news from MRI scan. GBM Tumor shrinkage from 4.5cm to 2cm

Happy New Year everyone. I wanted to give a positive news update as it is great motivation when there only seems to be negative news regarding glioblastoma. My dad had his 3 month MRI scan follow up (since the last scan in September) today and it shows tumor shrinkage from 4.5cm (in addition to swelling) down to 2cm and no swelling. 

What was added since the previous MRI scan (September) was starting these drugs in October:

• 16 mg dexamethasone and then slowly reducing to 2mg now; 
• Biweekly IV Bevacizumab - avastin ; 9 rounds completed; 
• 2g daily Valaciclovir - valtrex (1g in the morning, 1g in the night);
• 100mg daily Artemisinin;
• 500mg daily Astragalus. 

I think the Bevacizumab - avastin and Valaciclovir - valtrex really helped.

I want to share his treatment as I know there is no one cocktail list and it can be difficult to know what to take and also where to get the drugs or supplements. We began by taking the list of "A" drugs from the table which Stephen shared with us after I emailed him directly. Stephen also provided a link to the Ben William's and Richard Gerber's cocktail list. Since my dad is unmethylated we tried to follow Richard Gerber's cocktail list as closely as possible. We printed out the BT Cocktail list Stephen shared with us, modified it to the "A" drugs and printed this as my dads list to show his oncologists and GP with the dosage he was taking. We were lucky some friends were able to get chloroquine phosphate, Celebrex and melatonin over the counter in Spain. This meant we could start slowly adding drugs one by one before getting the GP to prescribe these drugs to my dad. His oncologist was happy for my dad to try whatever he wanted once he did the treatment they suggest - he was free to add any supplements or drugs once we provided the oncologist and GP with the cocktail list, dosage, purpose (this info from the cocktail list Stephen shared) and the date we added the drug and only one by one with two weeks apart. For the likes of Valaciclovir - valtrex we named the researchers who carried out the study and the publication and then our GP was happy to prescribe these drugs from our local pharmacy.

We check his drug interactions using drugs.com website. It allows you to enter the list of drugs and says potential side effects or which drug combinations throughout the day to avoid. We also get the pharmacist to make up weekly blister packs and they put his drugs into morning, lunch, evening and night - this service really helps us keep organise. We keep a day example of how the pharmacist previously made up the blister pack and hand that in to the pharmacist the following month so they remember - as even for the pharmacist its alot in the cocktail to remember.

We are attending 2 hospitals because one is a general hospital to deal with his seizures and it is 10 mins drive away and his oncologist/neurologist hospital are 15 mins away from our house - we are very lucky with the excellent healthcare in Ireland and that it is all provided for (consultation, MRI scans, surgery, radiation, chemotherapy, Bevacizumab - Avastin, prescribed cocktail medication, social worker, counselling, hospital stays, blood tests, tumor analysis).

We were taking N-acetylcysteine early on (it is a Glutamate transporter 1 (GLT1)) but we stopped as we read it might enhance the tumor growth - we do not know if it is good or bad to take??? I think the seizure drugs blog glutamate transport?

We also obtained Disulfiram but never added this to our cocktail as we do not know if it interacts with the seizure drugs??

We also were taking Ranitidine (75mg daily) but stopped this after reading about side effects combined with Bevacizumab - avastin. Although my dad never had any issues. 

We are also interested in adding more to the cocktail perhaps similar to the CUSP9rv3 clinical trial cocktail such as ritonavir. We are also continuing to do research on HAART/HIV antriviral treatment as apparently HIV patients in Brazil/Mexico did not get GBM's over a 20 year period. 

My dad needed to take Duclox for constipation during chemo but is fine now.

My dad does not follow a ketogenic diet but we do encourage him to have a vegan diet as much as possible low in sugar. However if he wants to eat biscuits, bread, chocolate etc he does - he loves Latte's and dark mint chocolate. He does not have any alcohol due to the seizure medication.

BACKGROUND:

• My father was diagnosed with Grade 4 GBM after a grand mal seizure 24th Feb 2019. Located in the left temporal lobe, around 3cm.
• He had a successful craniotomy on the 7th of March 2019. About 95% removed, at least all visible tumor was removed.
• He completed the 30 sessions of radiation/310mg TMZ. 17th April 2019 to 30th May 2019
• He then did 3 months of 5/23 400mg TMZ chemo. July-September 
• TMZ was stopped and been doing Avastin every 2nd Monday since 23rd September 2019 - today 13th January 2020 still doing.
• Some notes to point out: he was swimming the evening before he had his 1st seizure. He couldn't finish a pint of guinness that night and had some pins and needles in his right arm before sleep - he had no other symptoms to indicate this tumor before 24th February 2019. He had the seizure in the middle of the night. 7th March Surgery went really well and was chatting away normally 1 hour afterwards. To this day he has never had any pain or headaches. He had no side effects during radiation and chemotherapy apart from the seizure 5 weeks after it finished. 

Side Effects:

• 30th June 2019: About 5 weeks after 30 sessions radiation/chemo and after having daily tingling, we spent the day walking around the countryside for many hours. We had a 2 hour car journey and he was 2 hours late taking his Keppra (at the time he was only on 1g total in the day, 500mg morning and 500mg evening). That night he had 4 multiple seizures. He came through after the 1st seizure but he seemed to have panicked when he saw the paramedics that he went into the 3 other multiple seizures. The hospital induced him into a coma for 24 hours which we were not expecting. His Keppra dosage was increased to 2.5g a day and they added phenytoin 300mg in the morning. They also restarted him in dexamethasone 2 weeks 4mg and then 2 weeks 2mg.
• 4th September 2019: He had been having foot twitching since 30th June every night when sleeping. From the end of August he was starting to mix up people's names and words due to aphasia resulting from the edema. Hospital increased the Keppra to 3g per day, added Clobazam 10mg x 2 and 16mg Dexamethasone daily - which we have been reducing since September until now (18th Jan) where he is on 2mg Dexamethasone. His speech has now returned to 100% and no seizures  after adding Phenytoin, Clobazam. There was alot of swelling/looked like the tumor was very active by MRI and due to MGMT unmethylation the hospital stopped the TMZ and have now been giving him Bevacizumab - Avastin on Mondays every 2 weeks, 9 rounds so far.  Bloods are all normal and within range.
• October 2019: My dad took Zovirax tablets and then switched to Valtrex as it apparently has better bioavailability. For 2 weeks when he started taking this we noticed he broke out in large cystic type spots around his face and neck - it almost looked like his body was trying to get rid of toxins??? These spots went away after about 2 weeks after starting the Acyclovir treatment.

Daily Routine: He carries around Midazolam injections in case he was ever to have a seizure

MORNING:

1. 8.30am: Ensomeprazole 40mg (One tablet a day). Stomach protector for steroid

After Porridge (with seeds):
9am: Following medication all prescribed by GP 

1. Dexamethasone 2mg (One tablet a day). Steroid to reduce swelling
2. Ramipril 5 mg (One tablet per day). ACE inhibitor, Lower Blood Pressure, Prevents accumulation of Tumor associated Macrophages) 
3. Phenytoin - Epanutin 300 mg - (3 x 100 mg tablets all taken at this time. Anti-seizure
4. Clobasam - Frisium 10 mg (twice a day, 10 mg in morning, 10 mg at night) Anti-seizure
5. Levetiracetam - Keppra 500mg x 3 (twice a day, 1.5g in morning, 1.5g at night) Anti-seizure
6. Metformin Hydrochloride 500 mg (twice a day, 500mg in morning, 500mg at night). Diabetes and Immune booster
7. Valaciclovir - Valtrex 500mg x 2 (twice a day, 1g in morning, 1g at night) Anti-viral, HSV, VZV, EBV, CMV. Guanosine binds to cancer cell DNA and converted by viral thymidine kinase and host cell kinases to aciclovir triphosphate (ACV-TP)
8. Chloroquine phosphate - Avloclor 250 mg. (One tablet per day, 155mg active chloroquine base). Malaria. Inhibition of late-stage autophagy
9. Minocyline 100 mg (twice a day, 100mg morning, 100mg evening - one month on and switch one month off to use Mebendazole instead). Targets macrophage/microglia. Anti-seizure
10. Mebendazole Vermox 100 mg (twice a day, 100mg morning, 100mg evening - one month on and switch one month off to use Minocycline instead). 

After omelette (with garlic):

10.00am: Supplements. Mainly obtained from iherb apart from Turkey tail which is difficult to get in Ireland and we get via evitamins.

1. Boswellia NOW 500mg tablet. (1 of 3 tablets per day) Reduces edema
2. ECG (green tea extract) . Now 400 mg. Sensitizer to TMZ by GRP78 inhibition
3. Maitake D Mushroom Wisdom (600 mg tablets – 1 tablet per day). Immune
4. Curcumin. Doctor's Best (1000mg tablets – 1 tablet once per day but give other brands of Curcumin later in the day as this is not Longvida and difficult to swallow) Immune; STAT3 inhibitor
5. Multivitamins. Optimum Nutrition, Opti-Men. (1 tablet once per day)
6. Vitamin D3.  NOW (10,000 IU tablets – 1 tablet once per day). Cell differentiation; Immune
7. Mushroom supplement mix from Fungi Perfecti Host Defense Stamets 7 (Royal Sun Blazei; Cordyceps; lions mane; Maitake; reishi; Chaga; Mesima); Immune
8. Artemisinin. Doctor's Best (100mg tablets – 1 tablet once per day) Malaria and Direct Cytotoxicity, apoptosis

LUNCH:

After snack:

1pm: Medication prescribed by GP 

1. Celecoxib - Celebrex (200mg tablet) Arthritis and COX-2 inhibitor, Immune (PGE2 inhibition),  reduces edema

1pm Supplements:

1. Astragalus NOW (500mg tablet) Immune

TEA: (meal followed by a glass of Kombucha or Kefir)
After snack:

5pm:

1. Omega 3-6-9  Now Foods, 1200 mg - 1 tablet per day) From Borage, Flax Seed & Fish Oils Increased oxidative stress in tumor cells
2. Milk Thistle, Silymarin Now Foods, (300 mg tablet) Immune and liver support
3. Berberine Natural Factors, WellBetX (500 mg tablet).Glucose metabolism and Induces senescence of  cells by down regulating the EGFR-MEK-ERK signalling pathway
4. Boswellia NOW 500mg tablet. (2 of 3 tablets per day) Reduces edema
5. Curcumin. Protocol for Life Balance, Curcumin SLCP Longvida 400 mg and  Advanced Orthomolecular Research (AOR) Curcuviva 400 mg (80 mg curcuminoids and Nordic Naturals Curcumin Gummies Mango 200mg Longvida. Prefers the Nordic Naturals gummies. Immune; STAT3 inhibitor

EVENING:

9pm: Medication prescribed by GP 

1. Clobasam - Frisium 10 mg (twice a day, 10 mg in morning, 10 mg at night) Anti-seizure
2. Levetiracetam - Keppra 500mg x 3 (twice a day, 1.5g in morning, 1.5g at night) Anti-seizure
3. Metformin Hydrochloride 500 mg (twice a day, 500mg in morning, 500mg at night). Diabetes and Immune booster
4. Valaciclovir - Valtrex 500mg x 2 (twice a day, 1g in morning, 1g at night) Anti-viral, HSV, VZV, EBV, CMV. Guanosine binds to cancer cell DNA and converted by viral thymidine kinase and host cell kinases to aciclovir triphosphate (ACV-TP)
5. Atorvastatin 20 mg (1 tablet a day) Manage Cholesterol
6. Minocyline 100 mg (twice a day, 100mg morning, 100mg evening - one month on and switch one month off to use Mebendazole instead). Targets macrophage/microglia. Anti-seizure
7. Mebendazole Vermox 100 mg (twice a day, 100mg morning, 100mg evening - one month on and switch one month off to use Minocycline instead). 

9pm Supplements:

1. Resveratrol Now Foods, 200 mg,
2. Soy Isoflavones with Vitamin B6. Holland and Barrett Contains active daidzin, genistin and other isoflavones, phyto-oestrogens
3. PSK or PSP (Turkey Tail Mushroom/Corilus versicolor/Trametes versicolor) NFH Hot-Water extract Immune 500mg (obtained from Walmart) have backup from evitamins from Mushroom Wisdom. 
4. Probiotics; Garden of Life, Dr. Formulated Probiotics, Mood+ ( 1 tablet once per day); 16 strains  50 Billion CFU¹ (203 mg)
5. Boswellia NOW 500mg tablet. (3 of 3 tablets per day) Reduces edema
6. Spirulina powder mixed in with green juice

NIGHT:

11pm: Medication prescribed by GP

1. Melatonin 20mg; 

Useful links we used:

Ben William's cocktail: https://btcocktails.blogspot.com/2015/08/ben-williams-cocktail-profile.html

Richard Gerber's MGMT unmethylated cocktail: https://btcocktails.blogspot.com/2015/10/rich-cocktail.html

CUSP9rv3 Cocktail list (Neurology consultant DR. Marc-Eric Halatsch) https://clinicaltrials.gov/ct2/show/NCT02770378

Positive correlation between HIV antiviral treatment and low occurrence of glioblastoma https://www.researchgate.net/publication/266011045_Gliomas_and_brain_lymphomas_in_HIV-1AIDS_patients_reflections_from_a_20-year_follow_up_in_Mexico_and_Brazil

https://virtualtrials.com/survive.cfm

https://virtualtrials.com/noteworth.cfm

http://www.anticanceralliance.com/cusp-nd/

https://www.survivingterminalcancer.com/

https://clinicaltrials.gov/ct2/show/NCT02770378

https://www.frontiersin.org/articles/10.3389/fphar.2018.00218/full

https://www.canceractive.com/article/repurposing-old-off-patent-drugs-as-new-and-effective-cancer-treatments