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**Note that this a 'pre-print' article that has not yet been certified by peer review.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

Story of Tetiana from Ukraine (gliosarcoma GIV WHO)

Hi everyone.

This is my first record for your blog. At first, let me thank to Stephen and others who created this platform. It is a really good opportunity to discuss our stories and get a lot of important information.

I have some concrete questions. Although before I have to say few words about myself and my story due to rules of this community, as I realised.

Ok, let's start.

Free Supplements Available

My husband developed permanent pill fatigue a few months ago and I have the following supplements/meds to give away. Many are sealed, but a few are open so specify which you would like and whether you feel comfortable with open bottles. I prefer they go to someone who is under financial strain. I am happy to send to the first couple of people who respond with their mailing addresses.
Wishing you all a peaceful holiday season! Sharon


Life Extension Super R-Lipoic Acid 240 mg
Panacur C (Fenbendazole)
Hydroxycitrate--Solgar
Zinc 50 mg--Life Extension--opened and sealed
Shark Liver Oil 500 mg-- Solgar
Optimized Resveratol Life Extension--opened
EGCg 400 mg NOW
Mushroom Science Turkey Tail Coriolus Super Strength
Kyolic (Aged Garlic Extract/Lecithin)
Lycopene 10 mg--Puritan's Pride--opened
Sunflower Lecithin 1200 mg Softgels Now--opened
Optimized Curcumin 1000 mg Longvida --opened
Berberine 500 mg--Amazing Formulas
Melatonin 10 mg-- Nature's Best

Hi all and Merry Christmas,

My 23yo son was diagnosed with a Diffuse Astrocytoma, right frontal lobe.  Had an awake craniotomy on Oct 15.  According to Dec 6, MRI some may have been left behind due to location at/near motor cortex but surgeon also says could be inflammation or scar tissue.  Recommends starting 6 weeks radiation in January, followed by 1 year of chemo (Temodar). Wondering if anyone has ever delayed treatment.  Also, what supplements would you advise?  Do you take them during treatment?  I have searched through other posts but want to make sure I do the right thing according to his pathology report.  Thank you so much for your help!

Anatomic Pathology Diagnosis:

IDH-mutant, WHO 2016 grade II

IDH1 R132H positive

ATRX expression with focal loss

1p/19q NOT deleted

Molecular Diagnostics Results:

79 Gene Mutation Analysis - 1 Mutation Detected

IDH1:ENST00000415913.1:c.395G>A; p.Arg132His

TP53:ENST00000269305.4:c.818G>A; p.Arg273His

CDKN2B:ENST00000276925.6c.367C>T; p.Arg123Trp

PTEN deletion DETECTED

TERT gene promoter mutation NOT detected

MGMT promoter methylation NOT detected

EGFR gene NOT amplified

Hi everyone!

My 14 year old son, Eli, has recurrent, metastatic medulloblastoma. The disease is in his bone marrow and bones.

He was first diagnosed in May 2017. He had a resection, 30 rounds of radiation and 7 cycles of chemo (cyclophosphamide, vincristine, cisplatin, premextred and gemcitabine). Eli had no evidence of disease for 2 years.

His recurrence was diagnosed September 2019. He had 2 cycles of temozolomide, irinotecan and avastin before this was stopped due to progression. His CNS remains clear of disease with only bone and bone marrow involvement.

I am now trying to decide between 2 different treatment options. 1) ACT001 (otherwise known as parthenolide). This would be a stand alone treatment that has mixed responses from adult glioblastoma patients. 2) A new trial called SJELIOT which consists of either cyclophosphamide and prexasertib (CHEK1/CHEK2 inhibitor) or gemcitabine and prexasertib. This is a new trial targeted at relapse medulloblastoma.

I am also in touch with Care Oncology Clinic in London but due to Eli's age they can only advise and cannot take him on as a patient.

Does anyone have any advice for me please?

HAART Antivirals? Atorvastatin dosage?

My dad is on valtrex (valaciclovir/valacyclovir) daily and I noticed it is a guanosine analogue. I was wondering if anyone is taking HIV HAART treatment, such as tenofovir as well? It is a adenosine analogue and therefore I would imagine would work well to bind to Cytosine and Valtrex to Thymine in the cancer DNA? I would imagine antiviral drugs are limited if only 1 of 4 potential DNA base analogues is used? I know the CUSP9 protocol is using ritonavir but it is just used by itself - perhaps a cocktail of antivirals need to be used to combine with the cancer DNA?

Also we were wondering about Atorvastatin dosage as he is on 20mg a day but Care Oncology seem to recommend people are on 80mg a day? Do people get side effects on this dosage? Should we increase the dosage?

Background on my dad:

My father was diagnosed with Grade 4 GBM after a grand mal seizure 24th Feb 2019. Located in the left temporal lobe. 

He had a successful craniotomy on the 7th of March 2019

He completed the 30 sessions and then 3 months of 5/23 TMZ chemo. In September 2019, 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 Avastin on Mondays every 2 weeks.  Bloods are all normal and within range.


He was having trouble with speach and twitching in September time but this is now gone and he is back to 100% after adding Phenytoin, Clobazam and Dexamethasone

Daily:

Seizure drugs: 1.5g x 2 Keppra ; Phenytoin; clobazam daily. 
He carries around Midazolam injections in case he was ever to have a seizure but has only had 2 occassions this year.

2 x 2 mg Dexamethasone daily

Experimental Drug Cocktail (Ben Williams):

1g x 2 Valtrex (valaciclovir/valacyclovir); Chloroquine (155mg active ingredient); Celebrex 200mg; metformin 500mg x 2; 20mg Atorvastatin; ramipril; ranitidine 75 mg;  melatonin 20mg; 100mg mebendazole (1 month on/1 month off); 100 mg x 2 minocycline (1 month on/1 month off);

Daily supplements of multivitamin; 16 strain Probiotics; PSK; Maitake D; ; Mushroom supplement mix for brain (lions mane 300mg; bacopa 250 mg; reishi 150 mg; gotu kola 130 mg; ginko 120 mg); curcumin (longvida); vitamin D; ECG; Milk Thistle; Berberine; Boswellia; Resveratrol; Omega 3-6-9; Soy Falvonoids (geinistein); Astragalus; Artemisinin

Avastin or Lomustine to prioritize?

Hi, those of you who are on combined Avastin + Lomustine for recurrence and struggling with blood counts, what is your experience, which treatment your oncologist prioritizes in need?

My husband who is a 32 months survivor with multifocal GBM progressed during his 2nd radiotherapy and his doctor gave up on him stating that he had less than 1 month of life expectancy. But luckily he reacted well to Avastin and his serious symptoms disappeared within days after the 1st infusion.

Together with the 2nd infusion we added lomustine (90 mg / m2) and it messed up with his blood counts on week 4 and 6 so his oncologist postponed both treatments. Plus, a few days after the combination treatment he started having severe diarrhea that is still ongoing and it didn't improve on those 2 weeks when we paused Avastin. He became weaker and weaker gradually.

Shortly after finally receiving the 4th Avastin with delay, he ended up in the ER due to confusion and seizures that we didn't experience in the past 3 months at all. Seizures were the first signs of tumor progression back in April so now we're frightened. Methylprednisolone was doubled to 64 mg (equivalent of 13 mg dex), Keppra was increased to 3000 mg. Symptoms disappeared within 2 days. Emergency CT showed only a very slight swelling which is actually an improvement compared to the last MRI in late August.

Today we were on pins and needles to finally start the 2nd cycle of Lomustine (we're already in more than 2 weeks delay) after his blood work results came back as perfect (BP 220,000, WBC 6.8) but the oncologist advised "Don't risk Avastin."

Avastin is a palliative treatment while chemo can really help if someone has a good reaction to it (TMZ helped him for 2 years) so I don't understand why the oncologist put Lomustine on hold in favor of Avastin considering that it is very likely that the tumors are progressing again? What's the point in using Avastin if he still needs tremendous amounts of steroids, plus he lays in bed most of the day despite the treatment? Next MRI will be in early December.

By the way, we sourced Lomustine from India because the oncologist wasn't able to prescribe it due to local protocols. He is only allowed to prescribe it after the failure of Avastin so we're actually not depending on his decision, it's just not a wise thing to disagree with your doctor.

My main concern is that there's some evidence that no chemo is able to help after the failure of Avastin so I can't see the reason why to wait for further progression in order to continue Lomustine, providing that his blood counts are perfect at the moment.

Thank you for any advice that you can provide.

Low dose perampanel added to levetiracetam (Keppra)

Experience of Low Dose Perampanel to Add-on in Glioma Patients with Levetiracetam-uncontrollable Epilepsy

Abstract

After introduction of levetiracetam (LEV), treatment of seizures in patients with malignant brain tumors has prominently improved. On the other hand, we still experience some cases with LEV-uncontrollable epilepsy. Perampanel (PER) is a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoaxazolepropionate acid receptor antagonist that has recently been approved for treating focal epilepsy as a secondary drug of choice. Available literature reporting PER medication in patients with gliomas is still sparse. Here, we report our initial experience with glioma patients and report efficacy of adding low dose 2-4 mg PER to LEV in patients whose seizure were uncontrollable with LEV monotherapy. Clinical outcome data of 18 consecutive patients were reviewed. This included nine males and nine females aged 24-76 years (median, 48.5 years), treated for glioma between June 2009 to December 2018. We added PER to patients with LEV-uncontrollable epilepsy. Adverse effects, irritability occurred in two patients, but continuous administration was possible in all cases. Though epileptic seizures occurred in four cases receiving 2 mg PER, 17 cases achieved seizure freedom by dose increments; final dose, 2-4 mg PER added to LEV 500-3000 mg. Our study revealed anti-epileptic efficacy of low dose PER 2-4 mg as first add-on therapy to LEV in glioma patients who have failed or intolerable to LEV monotherapy. Low dose PER added on to LEV may have favorable efficacy with tolerable adverse effects in glioma patients with LEV-uncontrollable epilepsy.

https://www.ncbi.nlm.nih.gov/pubmed/31748440

Good day to all!

Maybe Stephen or some of the blog readers will be able to comment. I will be very grateful.
Two months ago my sister had a second operation (I wrote about this on this blog a while ago https://btcocktails.blogspot.com/2019/10/good-afternoon-stephen-and-all-thank.html), and in early November we did an MRI. The doctor said that the tumor did not grow, but there was perifocal edema, which is a consequence of radiation. Literally - "this is not the edema to be feared." He said that he could last up to a year and leave himself. According to the doctor, everything is normal. But she feels much worse than some time ago. She constantly sleeps, the left side of her body works worse (before the operation, neither her arm nor leg worked at all, and afterwards she got better), there is a squint. The symptoms are very similar just to the growth of edema, about the same as before the operation. We reduced dexamethasone after surgery and had already reached 24 mg to 3 mg, but yesterday the doctors decided to increase it to 4 mg.
Doctors also said that she had vestibulopathy (dizzy), salt in the ear. Low potassium. We started drinking Boswellia about a week ago to make it easier to leave dexamethasone, but somehow it did not help. But they took only 1 capsule (according to the instructions on the bank, 3 per day is needed), because we were told that it should also be added gradually. Maybe it was necessary to take 3 cupsules? Until recently, we did not want to raise dexamethasone again, and we are now very worried about the deterioration.
Tell me, please, is it really possible to leave dex in our situation and how to do it right? Raise the dose (which has already been done), stabilize the condition, and then again slowly reduce it (before, 0.5 mg per week was removed approximately)? How to remove / control edema?

Thank you in advance for responding!

Hi all,

a promising japanese study:

https://academic.oup.com/neuro-oncology/article-abstract/21/Supplement_6/vi4/5620161?redirectedFrom=fulltext

Does someone know if there is a possibility to get access to this treatment without taking part in the study?

All the best!

Hi,  I write again seeking advice.  I have very much appreciated comments/advice over the years and the expertise of those on this blog.  Unfortunately, for some weird reason I cannot respond to responses, but am very appreciative!
My 26 y/o son has had another recurrence of his IDH1+ secondary GBM in L frontal lobe..
To summarize his past history, he had an AA3 diagnosed when he was 18 y/o treated with GTR and proton therapy only (clinical study) and had 5 good years where he graduated from college (with honors), worked and started medical school.  His tumor recurred his 1st year of med school as a very small area of IDH1+ low mutation GBM  (unmethylated) treated with aggressive GTR and then started on BGB-290 and TMZ study.  He was on study from 4/18 thru 7/19.  He completed a year of med school successfully while on chemo, but pretty low doses of TMZ used due to anemia (needed a few transfusions).  A 3 mm "scar" seen on 5/19 scan grew into a large tumor by 7/19.  So, since not great options, we opted for immunotherapy given his hematologic issues with preceding therapy--he was enrolled in IL-12 + Veledimex +PD1.  His recurrent tumor was found to be hypermutated and now methylated (?)--so thought it turned out to be an appropriate choice. He had another GTR 8/19 with excellent neuro recovery.  His MRI showed a strong inflammatory response around meninges/spinal cord, which study group felt was due to treatment (and they were correct).  Anyway, MRI at 2 months after surgery showed a large L frontal lobe mass--thought was that it could be pseudoprogression, but surgical path showed all tumor (don't have final path yet).
So...he had another GTR (fabulous neurosurgeon) and has no obvious cognitive deficits (he is tutoring Latin grammar at the moment).  He starts radiation next week (has been 7 years since proton) and will likely still have immunotherapy and ...something else. (Immunotherapy--likely Keytruda which is FDA-approved for mismatch repair deficient tumors?)

His current neuro-oncologist seems excellent, but the question is what else?
Options that have been considered--olaparib--radiosensitizing and might work with IDH1
                                                       --CCNU--old standby--don't know how long will tolerate
                                                       --regorafenib--superior to CCNU in one study--fewer blood probs?

Interestingly, his tumor did not grow at all in the 2 weeks before surgery, so wonder if immunotherapy was starting to kick in, though I was told that tumor growth is not always linear.

I know that this history is long and somewhat technical, but also that there are some very knowledgeable people on this blog.  Any insights of those on immunotherapy, CCNU or regorafenib would be appreciated.  I would also be curious if anyone has been on olaparib--it was tolerated well with radiation in elderly patients in British study.

Thank you so much for any help you can give....Anne

A hopefully encouraging update

Hello all,

I hope to offer some feedback and encouragement to others on their brain tumour journey.

I have not long finished six and a half weeks' (33 fractions) radiotherapy with daily temozolomide. The first post-radiotherapy scan was far better than we could have hoped for. Although I have yet to see the scans, the oncologist said he was delighted and was struggling to see evidence of residual tumour (even though we understand that there was some left in the corpus callosum). He looked a little surprised, I might add. He is now rather more interested in the supplements I am taking than he was pre-radiotherapy!

My tumour: anaplastic astrocytoma right frontal lobe, WHO Grade III, MGMT methylated, IDH1 mutation positive, ATRX expression lost, p53 wild type, Ki-67 20-25%,

Supplements/Repurposed meds:

Boswellia extract (WokVel)`	999mg / day
Etodolac	600mg
Omeprazole	20mg od
Curcumin (Longvida preparation)	1000-2000mg
CBD oil	50mg+/day
ECGC (green tea extract)	Teavigo preparation, 1/day
Melatonin	20 mg before bed
Omega-3 fish oils (EPA, DHA)	3000 mg daily of EPA + DHA
Selenium	200 mcg daily
Vitamin D3; or Alfacalcidol .(prescription)	5000-10,000 IU daily Vitamin D3
Chloroquine phosphate	250 mg daily;

During radiotherapy I exercised 10-15 minutes twice a day on a bicycle rigged up to a turbo trainer.
Diet-wise: I tried to avoid big, carbohydrate-heavy meals, ate lots of nuts, seeds, eggs and fish, and salad/vegetables. My energy levels actually increased during the radiotherapy (!) (I think this may have been partly because I was still recovering from the surgery when the radiation started).

I would therefore say that the above regimen has stood me in good stead so far and happy to answer any questions on my experiences to date. I have just finished the first cycle of temozolomide (at a higher dose than that during radiotherapy).