Monday, 27 January 2020

ZIKV preferentially infects glioblastoma stem cells (GSCs) rather than neural precursor cells

I've been mentioning the Zika virus occasionally on the site.  I still believe it holds promise.

https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30471-0?rss=yes&elqTrackId=84dc183cdc1f4a7da27da42e22c829ca&elq=2aab77d3e8ef4f579bd04cd257deb989&elqaid=27141&elqat=1&elqCampaignId=10608#.XiknzVRAgGM.twitter

Saturday, 25 January 2020

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


Tuesday, 21 January 2020

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.

Saturday, 18 January 2020

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

            Sunday, 12 January 2020

            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.

            Tuesday, 24 December 2019

            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

            Monday, 23 December 2019

            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

            Tuesday, 3 December 2019

            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?

            Thursday, 28 November 2019

            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

            Wednesday, 27 November 2019

            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.

            Saturday, 23 November 2019

            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 ╬▒-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

            Friday, 22 November 2019

            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!

            Monday, 18 November 2019

            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!

            Tuesday, 29 October 2019

            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

            Monday, 28 October 2019

            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).

            Musella yahoo groups shutting down. New forum address

            Here is a message from Al Musella.  Please check out and support his new forum.

            This group is closing down as Yahoo no longer will provide groups. We are moving to forum.virtualtrials.org 
            Please register there and try it out!

            Tuesday, 22 October 2019

            Hi Stephen, hi all,

            i read good things about the photodynamix therapy, for example:
            https://www.ncbi.nlm.nih.gov/pubmed/25915500

            One question about that topic does not let me go: Would it be possible to use that technique after a "full resection" or as an conservation thearapy when there is no tumor visible?
            Don`t you think you could attack left over cells that way?

            Thank you for an response!

            All good!

            Wednesday, 16 October 2019

            Good afternoon, Stephen and all!

            Thank you so much for this blog, for the large amount of useful information that can be found here. This is very important for everyone who has faced such a terrible disease. We would like to tell you about our situation and we really look forward to your help, since we do not know at all what is best to do in our case. My sister (48 years old) was diagnosed with glioblastoma multiforme in April that affects affecting the insular lobe of the telencephalon and the right frontal lobe of the brain (IDH wild type; MGMT is unmethylated; ATRX obtained). At the moment, we do not have any other data on genetic mutations, a full genetic analysis will be available only after 3 weeks. 4 days after diagnosis, an operation was performed to remove the tumor, a resection of more than 95%. During the operation, a displacement of the neoplasm with affecting the pyramidal tract (about 8 mm) was found. On the third day after the operation, my sister was already perfectly normal, feeling quite satisfactory. At the end of May, a course of radiation therapy began, 6 weeks (TMZ 75 mg / m2 per day, concomitant radiotherapy 59-60 Gy). Immediately upon completion of the course, edema began to develop, tumor recurrence was recorded, and the condition began to deteriorate steadily. The size of the new tumor at that time was already slightly larger than the removed one. We attribute the deterioration of the condition to the consequences of therapy, since a month and a half from the operation to the start of therapy, everything was fine. As a result, the sister began to choke, it became difficult for her to walk and talk, constantly lacking oxygen. Dexamethasone 12-8 mg began to be used. In July, we had an MRI in one of the best clinics in Germany (where the first operation, radiation, chemotherapy was performed), as a result of which German doctors refused us and gave us a couple of weeks ... By the end of July, she practically stopped moving on her own, could only reach from the bed to the toilet and vice versa, her left arm was almost inactive. In August, we started using Optune, took a chemotherapy course (TMZ, 240 mg / m2 for 5 days). In early September, literally a day after the completion of chemotherapy, the condition became critical, she simply did not wake up in the morning. Doctors were able to perform a miracle, brought back to life. And they insisted on a second operation, which became, as it turned out, the last available opportunity to save her life (without an operation, it's a matter of days). The operation was carried out on September 13, the tumor was removed by 90%. Dexamethasone 3 days before surgery - 20 mg, now reduced to 5 mg. A biopsy revealed that the removed tissue is radiation necrosis. But doctors can not be sure about the remaining 10% - this is necrosis or nevertheless a tumor. After the operation, the sister successfully recovers, the doctors are satisfied with the process. Memory, speech, motor functions were not affected. Now she can take several dozen steps a day with support. Every day we work out with a fitness trainer, two days ago we started going to the pool and exercise on a stationary bike. A few days ago MRI was done, the tumor does not develop, the displacement decreased by half.
            And now the main thing. We need to decide on the next steps. We wanted to participate in poliovirus trials in the USA, but they refused (complex tumor location, low Karnowski score).

            Considered as options for participation in studies of the Canadian vaccine VAL-083 (interested, because its effect does not depend on MGMT methylation), the DCVax vaccine. But at the moment for us it is all inaccessible in connection with the functional state of the patient.

            In addition, immediately after the second operation, we sent the tumor material for the manufacture of the dendritic vaccine. Our neurosurgeon (who performed the second operation) spoke out against its use. But we still plan to try it. Avastin was abandoned, and in general, we are actively studying alternative medicine options, we want to make our own cocktail. But while we still haven’t figured it out enough, we don’t understand how to correctly compile it, what additional information is needed for this. It’s very scary to harm her! We are afraid of the traditional treatment, because before our eyes a person literally died away with its use. And now, every day, even small, but progress and improvement is noticeable. And we are afraid to make a mistake in the independent choice of funds - what if she suddenly gets worse?

            Do you believe in alternative methods in general or choose traditional treatment?

            Has anyone tried soda solutions, what do you think of this method?

            I understand that the question is very vague, that everything is very individual, and now I’m carefully studying all the information on the blog, but maybe you can recommend which drugs you should definitely pay attention to? What worked for many?

            We will be very grateful for your reply!


            Monday, 14 October 2019

            Feedback on Cocktail & Post-TMZ

            Dear Stephen, Dear All,

            I’m so sad that so many of us are finding ourselves here. You have my immense gratitude, Stephen, for the invaluable knowledge that you share with us all and for this incredible website.

            I was diagnosed with GBM in July 1018. I’m a single parent of a young child. This nightmare has been devastating.

            My tumor was very large, in my right parietal cortex, 100% resected. It was 94% MGMT methylated. It had TP53 mutations in three variants, no IDH1 mutation, CBL mutations in two variants, CDKN2A/CDKN2B homozygous deletions, Stag2 mutation, PDGFRA mutations in two variants (one with 85% frequency), and very high amplification of PDGFRA (~25,000 reads (>50x)) .

            I’m now completing my 12th TMZ maintenance cycle. I have not yet had a recurrence and know it’s a race against the clock. The tumor sample was unfortunately set in paraffin, so I’m not a candidate for DCVax-L. I’ve been trying to raise funds for the CeGaT peptide, but coming up with all that money is a longshot for me.

            1] Does anyone know if there are any other vaccines/immunotherapies for which I might qualify?

            2] I’m wondering if anyone could provide a recommendation of what treatment to pursue after a year of TMZ. I battled with my neuro-onc to use CCNU on day 1 of my TMZ maintenance cycles, but she would not relent. In fact, she has refused every request I’ve made of adding agents in addition to TMZ, such as Keytruda, to prolong my survival. Is my only option at this point in terms of ‘standard of care’ metronomic low-dose TMZ?

            3] Is there such a treatment as metronomic low-dose CCNU? If not, might I push to now receive CCNU in a conventional manner, assuming my blood counts are okay?

            4] If I proceed with metronomic low-dose TMZ, should I avoid low-dose metronomic Accutane?

            5] I had to stop high-dose Tamoxifen owing to concerning side effects. Would it have any value (such as for protein kinase inhibition) at a much lower dosage? Is there another effective anti-angiogenesis medication to use instead?

            Following is my current daily combination of off-label medications. I would so greatly appreciate any feedback on the dosages (are my current ones at therapeutic levels?) and what agents I might consider adding. Thank you so very much!

            Celebrex 400 mg
            Metformin 1500 mg
            DCA 1000 mg (on/off owing to significant neuropathy)
            Lansoprazole 30 mg (120 mg 3 days before TMZ, during, 2 days after)
            Chloroquine 250 mg
            Naltrexone 4.5 mg
            Minocycline 200 mg
            Melatonin 20 mg

            With gratitude and praying for us all!
            ~Joule

            Wednesday, 9 October 2019

            Intense itching. could it be due to a supplement?

            Advice and experience sought.
            Having completed 6.5 weeks of radiotherapy and daily temozolomide for a grade 3 astrocytoma, I started to develop fairly intractable itching - sometimes on my legs, arms or back (which is where it is currently). It started fleetingly while I was going through the treatment, so I assumed it was a reaction to temozolomide. My blood tests were all fine when I had my last dose of treatment. It's been over two weeks since my last dose of temozolomide and the itching is getting worse. I wondered whether anyone had experienced such symptoms with any of the following cocktail?
            • Boswellia (WokVel): 999mg / day
            • Vitamin D: 10,000IU / day
            • Curcumin (Longvida): 1000mg/day
            • ECGC (TeaVigo) Green tea extract 1/day
            • Melatonin: 20mg at night
            • Omega 3 Fish Oils: 3000mg daily of EPA +DHA
            • Chloroquine phosphate 250mg/ day
            • Selenium: 200mcg/day
            • Etodolac: 600mg/day
            • CBD oil: 50mg+ / day
            I'm going to see my family doctor to check whether it is anything obvious, and to get kidney and liver function blood tests done.

            Any other ideas or suggestions?

            Monday, 7 October 2019

            URGENT: my son of 6. Help needed with decision and protocol


            Dear friends,

            I have a very delicate  and urgent decision to make tomorrow and i would love to hear what you think. I think nobody can understand us better than you.

            My son of 6, Dario, is diagnosed with an aggressive brain tumor called AT/RT in the 4th posterior fossa. At the time od diagnosis he had a M1 metastasis consiting of cells found in the spine. After this diagnosis all the spine test were negative (done every month). He had surgery in may 2018 and we followed the sickkids protcol for a year and a few months (6 cycles of chemotherapy and maintenance protocol consisting of tamoxifen)

            After 1.3 years he relapsed this last 29 august and he had again surgery with total resection. The tumor came back in the same.

            After the relapsed i started to devour all the literature and find these non conventional approaches and researches like Daniel from cancertreatmentresearch.com who are helping us.

            We started a off label drugs cocktail that i have pasted bellow.  We are following this religiously. And we are triying to improve it. A pediatric doctor and some other researches are helping us to find dosages etc

            The MRI two weeks ago is clean and the CT scan from thursday is clean but since we have not done any chemo or radio after surgery, we are nervous.

            Our oncologist at the hospital only recommend at this point doing full brain and spine proton irradiation (54gy in the tumor bed) and 34gy in the spine and rest of the brain.

            For a kid of 6 year this is not the best treatment but it is also an aggresive cancer. So most of the standard oncologist and radiologist will recommend this standard treatment. We never did radiation before.

            So, my line of thinking is untill now:
            Let's do focal radiation  only and give him the opportunity to avoid serious side effects of the full brain and spine irradjatiob and if the tumor comes back, we are using the off-label drugs and a second irradiation only to where the tumor if it comes. 

            I am still in doubt, my wife too. I do not know i we are risking his life or not. If we do not irradiate the whole brain, there is the risk of dissemination because he already had M1 at diagnosis and after one month he has not received any chemo or radiation. 


            I don't want to make you responsible of giving your opinion because we are the ones responsible but i am not sure if the tumor come backs we can fight it with the "off-label drugs". Since it is aggressive and comes very fast, i do not have experience what you could have had in brain tumors or your collegues in this world of non-conventional treatments. There is also metronomic treatments or alisertib for re-ocurrences. 

            Please, help me. I will never make you responsible of any suggestion but you have seen many cases already of this type, can you comment what is your view? what will you if it was your son?
            I am trying to give him an opportunity to avoid the big side effects of total radiotherapy but at the same time i am not sure if we are risking his life.
            We have time and resources to dedicate for him.

            This is what we are following now:

            ===
            PROTOCOL



            Main drugs used now:

            1.  METFORMIN 500mg 1/2 pill after breakfast daily for 2 weeks if tolerated increase to 1 pill after breakfast daily     
            2. MEBENDAZOLE 200mg 1 pill after lunch daily
            3.  ATORVASTATIN  or sinvastim 10mg 1 pill at bedtime
            4.  DOXYCYCLINE 100mg 1 pill after dinner for 30 Days EVERY 3 MONTHS, to start after 3 MONTHS. 
            5.  TAGAMET (CIMETIDINE) 200mg 1 pill once daily {PLEASE DO NOT TAKE WITH ANY OTHER MEDICATIONS, VITAMINS, OR SUPPLEMENTS} 
            6.  CLARITIN (LORATADINE) 10mg 1 pill once daily
            7.  NICLOSAMIDE 500mg 1 pill once daily THREE TIMES WEEK ONLY (we have not started this drug) 
            8.  IBUPROFEN 200mg 2x/day after food (PULSE THERAPY which means doing this periodically for 2-3 months at a time with breaks of 1-2 months. We have not started this one)
            9, Oral etoposide (we started this one 2 days back)

            Drugs that will being considered depending on outcomes and safety of use:
            1. Ribavirine. 200 mg. 
            2. Disulfiram modulates stemness and metabolism of brain tumor initiating cells in atypical teratoid/rhabdoid tumors https://academic.oup.com/neuro-oncology/article/17/6/810/1113353
            3.  6-diazo-5-oxo-L-norleucine. Unbiased metabolic profiling predicts sensitivity of high MYC-expressing atypical teratoid/rhabdoid tumors to glutamine inhibition with 6-diazo-5-oxo-L-norleucine https://clincancerres.aacrjournals.org/content/early/2019/07/12/1078-0432.CCR-19-0189
            4. Dasatinib and nilotinib
              differential methylation of a PDGFRB-associated enhancer confers specific sensitivity of group 2 ATRT cells to dasatinib and nilotinib, and suggest that these are promising therapies for this highly lethal ATRT subtype. https://www.cell.com/cancer-cell/pdf/S1535-6108(16)30509-8.pdf https://www.ncbi.nlm.nih.gov/pubmed/27960086
            5. Sustained Complete Response to Metronomic Chemotherapy in a Child with Refractory Atypical Teratoid Rhabdoid Tumor: A Case Report https://www.frontiersin.org/articles/10.3389/fphar.2017.00792/full
              Continuous oral celecoxib with alternating metronomic etoposide and cyclophosphamide, in combination with biweekly bevacizumab and monthly intrathecal liposomal cytarabine
            6. Inositol tripuorosphosphate. Method of reducing multi-drug resistance
            7, Phenylbutyrate to Treat Children With Progressive or Recurrent Brain Tumors https://clinicaltrials.gov/ct2/show/NCT00006450.  
            9, valganciclovir  A Swedish study used a loading dose, followed by a maintenance dose. The loading dose was 900 mg orally twice a day for three weeks, followed by 900 mg a day. Valcyte tablets come in 450 mg tablets so that would be 2 tablets in the morning and in the evening for 3 weeks and then 2 tablets in the morning thereafter every day
            10.
            chloroquine/mefloquin
            11. clemastine


            SUPPLEMENTS used now

            8.  CURCUMIN 400mg 1 pill 2x/day 
            9.  BOSWELLIA 400mg must be a minimum of 3000mg per day (8 pills per day)
            10.  VITAMIN D 3000 IU once daily
            11.  PROBIOTIC once daily
            12.  ASHWAGHANDA 500mg 1 pill 2x/day
            13.  MUSHROOM EXTRACT 2x/day 
            14.  MILK THISTLE 175mg 1pill once daily
            15.  ASTRAGALUS 500mg 1 pill 2x/day [During Radiation Increase to 2 pills 3x/day]
            16.  URSOLIC ACID 50mg once daily hay 150
            17. CBD-THC. 1:1 ratio. 

            Supplements that are being considered:
            c) Canagliflozin https://www.cancertreatmentsresearch.com/glucose-absorption-inhibitors-to-inhibit-tumor-growth/ The purpose of using this one is to lower the amount of glucose absorbed by the tumor
            D) Honokiol. Eliminates Glioma/Glioblastoma Stem Cell-Like Cells Via JAK-STAT3 Signaling and Inhibits Tumor Progression by Targeting Epidermal Growth Fac..https://www.ncbi.nlm.nih.gov/pubmed/30587839/
            d) Fish oil. 1000 mg (w/ any meal, unless PLT < 125)
            E) Artemisia annua 
            f) Melatonine, 5b (built gradually)
            g) Digestive enzymes (with each meal)
            H) Essiac (night)
            i) Selenium, 50-75mcg 


            Thanks in advance
            Óscar