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

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 alone?

Further to a recent previous post.

3 months of TMZ 5/23 showed that chemo is not working for unmethylated GBM. The tumor is very active according to MRI comparison between July and September 2019. There was alot of swelling which is currently being reduced with 16 mg steroids per day in the past week. Speech has improved alot with this. Was told it is too close to previous radiation or surgery to have either done again.

2 weeks ago clonazepam was prescribed 10mg x 2 and Keppra increased to 1500mg x 2 and Phenytoin 300mg in the morning -  all of this is keeping seizures, twitches and focal seizures away.

Oncologist is going to start IV Avastin today and stop all treatment - asked if it was pallatiative but answer no it is not pallatiative treatment yet. Thought it was unusual to go ahead with Avastin by itself and not combine it with another chemo treatment such as lomustine?

Have been following cocktail since during radiation treatment back in April 2019 which I posted about in previous post. This includes daily chloroquine (155mg active ingredient); celebrex 200mg; metformin 500mg x 2; Atorvastatin; ramipril; ranitidine 75 mg; mebendazole; melatonin 20mg.

Also the usual daily supplements of mulitvitamin; 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)

Wondering if anyone has any experience of just Avastin being prescribed? I am wondering what is even the point in doing avastin alone? Appears to have more side effects and very little extra benefits, or OS? I was optimistic that Richard Geiber had Avastin and low dose TMZ but that doesnt seem to be on offer to us? Or any chemo alternative?

Very disappointing TMZ stupps protocol + cocktail did not seem to work. 

Cocktail question, Fluoxetine or Celebrex?

Dear Stephen and all,

I have a question concerning my girlfriend's father. He is 57 years old. He was diagnosed with a Grade IV, MGMT unmethylated Glioblastoma in the left occipital lobe, September 2018. After the surgery, he received radiotherapy and chemotherapy using VAL-083 in China during 08/11/2018 - 27/06/2019. He had an MRI scan on 20/08/2019 and there is a 17mm*10mm GBM recurrence in the left temporal lobe.

Now his oncologist suggests receiving the standard 5/23 Temozolomide treatment. Since his GBM is MGMT unmethylated, we want to have the cocktail to enhance the performance of Temozolomide for him. He is taking Metformin, Verapamil, Chloroquine and Keppra. We want to choose 1 more medicine from Fluoxetine and Celebrex, which one is better?

Thank you for your help! Best wishes to everyone.

Details of the condition of my father are listed below:

• On 28/09/2018 he had surgery due to a tumor in the left occipital lobe. According to the biopsy, he was diagnosed with a Grade IV Glioblastoma Multiforme, MGMT unmethylated, ki67 70%, IDH1/2(-), 1p/19q non-codeleted, non-diffuse.
• On 08/11/2018, he began to receive radiotherapy and chemotherapy using VAL-083 with a dose of 30mg/m2 IV. But soon he suffered severe myelosuppression and both radiotherapy and chemotherapy are stopped for 2 weeks. After that, the dose of VAL-083 was tuned to 20mg/m2.
• On 24/06/2019, the assessment via MRI is CR I class, complete response (that shows the VAL-083 is effective for him)
• On 27/06/2019, he finished the clinical trial, including 10 cycles of treatment using VAL-083.
• On 20/08/2019, MRI shows that there is a 17mm*10mm enhanced mass in the left temporal lobe (the original tumor was in left occipital lobe).

Cocktail for Yara’s father / help with drug side effects / 30% PD-l1 expression

Hello my dear friends and partners!

I had many doubts and I still have them despite of reading much.
And I decided to ask for your help at least.

My father had surgery 4 month ago. Chemoradiation finished 1 month ago. Left side of brain was damaged. He has Glioblastoma.

He has problems with speech and memory now.
That is why it is too hard to establish the cause of some uncomfortable and bad feelings after taking medicines and CAMs… He can not describe it correctly and can not remember when it was started for example…

---------He has no mgmt/idh1/braf/msi
---------He has 30% PD-l1 expression.
---------MRI shows continued growth (mono TMZ was not effective).

This month we started:
avastin+TMZ (5+23, 400 mg)

It is risky because TMZ did not worked well before. But I found it can do other work: reduce PD-l1 expression. And decided to use PSP(PSK) Oriveda together (6 pills =5 days with TMZ, 2 pills other days).

!) MAIN QUESTION: is this mechanism can work or not?
https://www.ncbi.nlm.nih.gov/pubmed/30709339

!) SECOND QUESTION IS: he is getting shakes. What can it be?  (inside based like fever). But temperature is ok. Blood pressure is pretty normal. Pulse is ok.
Problem is – he can not remember when it was started (may be after avastin). It was more than 1 time. He is hiding his condition may be…
And he sleeps much.

These supplements was added (after radiation/before or together with new chemo):
avastin (1 in 2 weeks) +TMZ (5/23)
++++++ melatonin 20mg only 5 days (or need to use all time?)

---------1) alpha lipoic acid (2x300=600)
---------2) curcubrain (1x400=400)
---------3) PSP(PSK) Oriveda (2x350 = 700  or 6 at TMZ days)
---------4) Carvedilol for pulse (1/2)
---------5) started to change carbamazepine (200mg) to keppra (250mg) – TOGETHER 1 week. Then more keppra less carb.

PS – keppra for unmethylated MGMT (still risk if TMZ not working)

Help me to connect his fever/shake with suppliments.
I can guess 1) it is avastin 2) keppra together carbamazepine 3) may be PSK/PSP… But may be you know bwtter?

Also he is taking (from the beginning)

---------metformin (1500)
---------Boswellia (2000)
---------D3 (4000)
---------Omega3 (1500)
---------allopurinol
---------Losartan
---------Nifedipine
---------Aspirine low dose

He has diabetes 2 type/hypertonia/


-----------What can I add or remove? (may be malatonin all days not only 5)? may be lower dose TMZ/ methronomic or replace TMZ with Irinotecan? (to not risk with combinations).
------------Is my combinations effective (TMZ+melatonin+PSP+keppra) with our mutations? (add/remove?)
------------What can be the reason of weakness and shake/fever?
------------Do you have link for Japan protocols (psk/psp)?
Thank you!

Temozolomide + mifepristone in rat glioma model

• Mifepristone, an FDA and Health Canada approved antiprogestogen, used to induce abortion.

• C6 rat glioma cells implanted into brains of male Wistar rats
• temozolomide applied to the rats at a dose of 5 mg/kg/day intraperitoneally
• mifepristone applied to the rats at a dose of 10 mg/kd/day subcutaneous injection
• rat survival as show below ("sham" refers to rats undergoing sham surgery with no glioma cells implanted)
• combination of temozolomide + mifepristone was effective where either single agent alone was  ineffective

Full study links here: https://www.mdpi.com/2072-6694/11/1/16

Optimizing TMZ

My 64-year-old husband was diagnosed with GBM in his left temporal lobe after a successful resection in 1/2016. His tumor is unmethylated and IDH negative. He is TMZ-naive and has been on Keytruda and Optune for a year. The tumor was stable until late October, when it extended into a new area.  It is slow-growing according to a PET scan yesterday.

Genomic testing of tissue retrieved from a second resection 11/16 highlighted mutations in NF1, PTEN, ASXL1, HNF1A, MLH1, NOTCH1 and SPEN. My husband's NO suggested Temsirolimus because of the PTEN mutation and TMZ starting in January.

My big research question is how to get the most kick out of TMZ, given his methylation status. It seems that either daily or 7-day/alternating Temodar have better clinical results than the standard protocol. I also wondering how best to sensitize GBM cells to TMZ and potentiate the treatment. Different studies suggest adding:
- Tamoxifen
- MGMT inhibitor O6-benzylguanine (O6-BG)
- Interferon-β (IFN-β)
- oncolytic adenovirus
- excision repair pathway enzyme apurinic/apyrimidine endonuclease/redox factor-1 (APE)
- Prozac/Fluoxetine
- antabuse/disulfiram
-Metformin

This all makes my head swim. Have any of you tried an alternative TMZ dosing schedule along with something to enhance its effectiveness against a unmethylated tumor?

Thanks for all your information and help.

PCV vs Temodar in IDH1 mutated unmethylated astrocytoma

There must be a lot of people who have already dealt with this issue but I didn't see any discussions on it.

I'm 47 years old with a recurrent grade 2 Astrocytoma previously treated with surgeries. Just over 12 years ago it was also treated with radiation, but not with chemotherapy. It's IDH1 mutated, unmethylated and 1p/19q are intact. I'm deciding between radiation followed by PCV or radiation with Temodar and adjuvant Temodar.

The results of RTOG 9802 make PCV appear to be a reasonable option, but RTOG 0424  Temodar results are just as good. My doctor's say Temodar will be as effective as PCV and more tolerable. The advantages of PCV are: the RTOG 9802 survival plot for IDH1 mutations looks good, it's a multi-agent treatment, the methylation status isn't a factor, and there seems to be less risk of hypermutation.

Has anyone with similar tumor characteristics chosen PCV over Temodar, if so what influenced your decision and how did it work out?

Hi,

I'm updating this discussion for anyone in the future who might be interested.

I've had the 3 opinions below.

UCSF:

They didn't give me any new information about hypermutation. Results of trials will be released in 3 or 4 years.

They confirmed my diagnosis and recommended SOC with 6 cycles. They said there was no information more cycles or a different dose schedule provided any benefit. I wasn't eligible for the Everolimus or the other 2 trials for low-grade tumors.

UCLA:

This is where the recurrence was initially diagnosed.

They recommended SOC. With the following expected response rates for patients similar to me

50% without radiation.

75% response rate with radiation.

I didn't get a definition of response, but I think it means either shrinkage or cessation of growth.

Said there's no data to indicate the ketogenic diet helps, but it won't hurt

UCSD:

Confirmed diagnosis.

Said preliminary study results indicate Temodar works about as well as PCV.

10 or 15 % experience hypermutation.

12 cycles recommended.

Most tumors cease growing and about 15% of patients see a reduction in tumor size.

MGMT is less important in low-grade tumors than high-grade tumors.

IDH1 mutated tumors are more chemosensitive.

Treatment: I decided to go with proton radiation + Temodar. I can always change my mind after radiation if new information indicates switching chemo is best. I'm also taking various supplements and started the ketogenic diet.

I had my first proton and Temodar yesterday and woke up surprised by how much it affected me. Symptoms included: fatigue, headache, and I threw up after only 3 sips of coffee. An extra Ondanestron cleared up the nausea after about 1/2 hour.

BGB-290 (brain penentrant PARP inhibitor) trial now open in USA

Formerly this drug was only available in 2 Australian clinical trials.  A trial has now opened in the USA (Arizona, Colorado, Tennessee, not yet open in Oklahoma) for newly diagnosed GBM with unmethylated MGMT, or for recurrent GBM (methylated/unmethylated MGMT), combined with standard treatments (temozolomide + BGB-290 in the recurrent group).

https://clinicaltrials.gov/ct2/show/NCT03150862

Past post that mentioned BGB-290 and PARP inhibitors.
http://btcocktails.blogspot.com/2017/07/parp-combination-therapy.html

PARP combination therapy

Hello all,

I came across this article:

PARP inhibitor combination therapy

"Here, we summarise both the pre-clinical and clinical evidence for the utility of such combinations and discuss the future prospects and challenges for PARP inhibitor combinatorial therapies."
http://dx.doi.org/10.1016/j.critrevonc.2016.10.010

Does someone have experience regarding PARP combination therapy? I know this has been discussed before in other posts especially when a tumour is IDH1-mutated. In the article they also propose that MGMT methylation is positive factor for PARP therapy.

It would be interesting to see results from trials or hear personal experiences on PARP therapy.

All the best,
Juha

Expanded Access to VAL-083

https://clinicaltrials.gov/ct2/show/NCT03138629

"This is an expanded access program (EAP) for eligible participants. This program is designed to provide access to VAL-083 (dianhydrogalactitol) prior to approval by the local regulatory agency. Availability will depend on territory eligibility. Participating sites will be added as they apply for and are approved for the EAP. A medical doctor must decide whether the potential benefit outweighs the risk of receiving an investigational therapy based on the individual patient's medical history and program eligibility criteria."

There is also an upcoming phase 3 clinical trial that will test VAL-083 for recurrent GBM that failed Avastin.

https://clinicaltrials.gov/ct2/show/NCT03149575

Agents for MGMT Unmethylated, PTEN Mutation, and PDGFRA Amplificayion

Hi,


My mother got the GBM surgery on Feb 6 this year. She is MGMT unmethylated, PTEN mutation, and PDGFRA amplification.


Does any one know effective agents for treating these disorders or symptoms?


Regards
James Zhou

Keppra and Temozolomide

Hi Everyone!

I'm new to this blog. I've read many posts and this is a great help to me, as I'm a beginner in the drug coctail treatment.

Our story briefly:
1) My father, 55, was diagnosed with an unknown brain tumor in October 2015 (the biggest dimension 43 mm). Craniotomy was carried out 3 days after the diagnosis. Preliminary histopathology - astrocytoma III, final result - glioblastoma IV.
2) First MRI after the surgery in December, right before chemoradiation, showed still a big tumour. According to the oncologist - radical recurrence. According to another neurosurgeon (we consulted the MR image in another hospital) - first craniotomy improperly done (!!). I'm not sure who's right... the other neurosurgeon, specialized in gliomas, was very convincing.
3) We decided for another surgery (by another surgeon). The resection must have been deeper as afterwards my dad's sight is worse (he sees everything darker, has problems with reading, seeing details etc., however he's getting better, it's been 6.5 weeks since the surgery).
4) Now chemoradiation. First cycle of Temodal during radiation for 42 days on a daily basis.
5) Tumour unmethylated, IDH1 negative. Other genetical tests of a frozen sample in progress.

We are at the very beginning of the drug&supplements treatment. It's very difficult to collect all the prescribed drugs. We're located in Poland. Started like that:
Temodal (150 mg/day);
Depakine (valproic acid) 2x500mg/day- prescribed by the neurosurgeon to prevent seizures;
Keppra (will start tomorrow, 2x500 mg/day)- added in order to sensitize the tumour for TMZ (prescribed by our GP on request, she agreed);
Dexamethasone (2 mg/day);
Proton pump inhibitor (1x/day) - drug called IPP20 in Poland;
"Pheonix tears" with high THC and CBD (rectal application) - 2 ml/day
Curcumin (up to 3000mg/day)
Quercetin
Vitamin C (1000 mg/day)
Sugar-free diet and radical reduction of meat. Working on reduction of gluten.


I have one question and would be grateful if anyone could advise sth:
What would be the best scheme of taking Keppra to sensitize the tumour for TMZ. Does it matter, if the first doze (500mg) is taken with Temodal on an empty stomach or he can take it later, after his daily radiation (with a meal afterwards)?
Should we add Prozac and Disulfiram, apart from Keppra, for a better chance of TMZ working?


Cheers!
Piotr

Rich cocktail

 I think we never posted Rich cocktail. That one is especially important for people with unmethylated tumors.

Stephen W edit: 
this info was taken from page 2 of the Glioblastoma...Our Cocktail & Story thread at Cancer Compass. The post is dated November 13, 2013.  The "if I were to do this again" part at the bottom is therefore not necessarily accurate today, but we will let Rich make changes as he sees fit.


- Temodar (temozolomide), 80mg/day (calculated by 40mg/m**2/day)
- Avastin (bevacizumab), 10mg/kg at 21 day intervals

- Chloroquine Phosphate, 250mg/day

- Celebrex (Celecoxib), 600mg/day

- Verapamil, 480mg/day

- Accutane (13-cis-retinoic-acid), 160 mg/day, 14 days on, 7 days off

- Tagamet (cimetidine), 800mg/day

- Melatonin, 20mg/day

- Coriolus versicolor extract PSK/PSP, 3g/day

- Maitake-D mushroom extract, 1200mg per day

- Reishi mushroom extract, 2.5g per day

- Resveratrol,  20mg per day

- Green Tea Extract, 4g per day

- Selenium, 200mcg per day

- Soy Extract, 5g per day

- Fermented Papaya Extract, 1000mg/day

- Silibinin extract, 2g/day

- Curcumin/tumeric extract: 800mg/day

- Gamma-Linolenic Acid (GLA) Extract, 3g per day

- Omega-3 Fish Oil Extract, 3gm per day

- Fresh aloe vera (drink/mixed aloe, water, honey and grappa),1 cup/day

- Standard multivitamin capsules, time-release

- Vitamin D, 10,000 IU/day

- Aspirin, 200mg per day

- Brewed Green Tea, aprox. 2 liters per day

But if I were to do this again, I would now also consider adding (at least) the following:

- Metformin, which regulates uptake of glucose

- Disulfiram, which inhibits p-glycoprotein extrusion pump and block glioma cell signal pathways

- DCA, which inhibits glycolysis

- Valproic acid (depakote), a known HDAC inhibitor, and potentially reactivates p53

- Chlorimipramine, which selectively blocks glioma mitochondrial function

IDH Wild-Type GBM

I''ve copied over the addendum path report for my husbands tumor.  I haven't been able to find any promising treatment throughout my research for his tumor type and feeling quite desperate!  Any suggestions based on the additional information we have...I'm not liking what I've read so far and the outcome doesn't look good....

Comment This case was subjected to IDH1/2 mutation analysis performed at Moffitt. It was also sent for MGMT promoter methylation testing, for FISH testing of chromosomes 1 and 19, and of chromosome 10  (PTEN locus), as well as for EGFR vIII assessment. No IDH1 or IDH2 hotspot mutation was found by sequenom. MGMT testing was negative for methylation of the gene promoter. FISH testing was  negative for codeletion of chromosomes 1p/19q, but positive for monosomy of C10 at the PTEN locus.  The EGFR vIII deletion was negative. In addition oncogene testing by Next Generation Sequencing was  performed at Moffitt and reported separately; in summary, no mutation was found in the assessed  genetic 'hotspots'. The findings are characteristic of IDH-wildtype glioblastoma. The histopathologic  diagnosis and interpretation are unchangedAddendum Pathology Report
	RIGHT TEMPORAL TUMOR Addendum IDH1 AND IDH2 MUTATIONAL STATUS: - NEGATIVE FOR IDH1 AND IDH2 MUTATIONS BY SEQUENOM 1p/19q STATUS: - NEGATIVE FOR 1p/19q CODELETION BY FISH MGMT PROMOTER METHYLATION STATUS: - NEGATIVE FOR MGMT PROMOTER METHYLATION PTEN/CHROMOSOME 10 STATUS: - POSITIVE FOR PTEN/C10 LOSS BY FISH EGFR vIII STATUS: - NEGATIVE FOR EGFR vIII NGS TRUSIGHT HOTSPOT MUTATION ANALYSIS: - NEGATIVE FOR ACTIONABLE MUTATIONS Any help would be much appreciated!

Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter

http://neuro-oncology.oxfordjournals.org/content/early/2015/09/14/neuonc.nov198.extract

Will add to the brain tumor Library.

Quote from Hegi and Stupp:

"Together, the data allow the conclusion that alkylating agent chemotherapy is of marginal benefit, if any, for patients with MGMT unmethylated GBM. By continuing to treat the majority of MGMT unmethylated patients with TMZ, we are missing an opportunity to do better."

Keep in mind that this was written by the lead investigators of the 2005 trial that led to TMZ becoming standard of care for newly diagnosed GBM.  The writing is on the wall.  Soon there will be two standards of care for ndGBM based on MGMT status.  It make take a few years, but patients with unmethylated MGMT status deserve something better.

However, this editorial did not consider the potential to sensitize these tumors to TMZ using agents that inhibit MGMT, or the potential of metronomic schedule TMZ in cases with EGFR overexpression. I wouldn't suggest abandoning TMZ altogether for these patients, but the current protocol does need to be tweaked for these patients (obviously).