Dexamethasone limits benefit of Immune checkpoint blockade

 New study published in clinical cancer research:

Concurrent Dexamethasone Limits the Clinical Benefit of Immune Checkpoint Blockade in Glioblastoma

https://pubmed.ncbi.nlm.nih.gov/33239433/

from the abstract:

Results: Despite the inherent responsiveness of GL261 to immune checkpoint blockade, concurrent dexamethasone administration with anti-PD-1 therapy reduced survival in a dose-dependent manner. Concurrent dexamethasone also abrogated survival following anti-PD-1 therapy with or without radiotherapy in immune-resistant CT-2A models. Dexamethasone decreased T-lymphocyte numbers by increasing apoptosis, in addition to decreasing lymphocyte functional capacity. Myeloid and natural killer cell populations were also generally reduced by dexamethasone. Thus, dexamethasone appears to negatively affect both adaptive and innate immune responses. As a clinical correlate, a retrospective analysis of 181 consecutive patients with IDH wild-type GBM treated with PD-(L)1 blockade revealed poorer survival among those on baseline dexamethasone. Upon multivariable adjustment with relevant prognostic factors, baseline dexamethasone administration was the strongest predictor of poor survival 

Conclusions: Our preclinical and clinical data indicate that concurrent dexamethasone therapy may be detrimental to immunotherapeutic approaches for patients with GBM.

The GL261 referred to is a mouse model of glioma.

Celebrex post-Avastin?

Hi all,

My brother received his first Avastin treatments over the past few months and suffered a brain bleed. After he was stabilized, his NO said we needed to take a break from Avastin and re-evaluate after 1 month. James was also on Xarelto during this Avastin treatment due to a blood clot that formed in his leg. He is no longer taking Xarelto.

James desperately wants to get off of steroids and is beginning to dose down. He's previously done OK dosing down slowly, but I wanted to ask about introducing Celebrex.

I'm concerned that maybe it could be a bad idea due to the brain bleed? The bleed has not fully "absorbed" so it is still present, though it is under control.

Any previous experiences or references would be greatly appreciated.

Thanks!

Baseline corticosteroids reduce activity of PD-L1 blockade

https://www.ncbi.nlm.nih.gov/pubmed/30125216 
Impact of Baseline Steroids on Efficacy of Programmed Cell Death-1 and Programmed Death-Ligand 1 Blockade in Patients With Non-Small-Cell Lung Cancer

http://sci-hub.tw/https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30666-1/fulltext  (summary of study published in the Lancet)

"Baseline corticosteroid use was associated with decreased overall response, and shorter median progression-free survival and overall survival in patients who received the equivalent to 10 mg prednisone or more per day at the start of the PD-L1 blockade."

10 mg of prednisone is equivalent to only 1.6 mg of dexamethasone.

http://clincalc.com/corticosteroids/

help with Dex effects

my husband had a second recurrence at the end of May.  Further surgery is not an option (he had awake craniotomy with Gliolan in February for first recurrence, so we were very disappointed that it came back so quickly).  He has been on 16mg per day of dexamethasone since May 30.  We are trying to make the most of every day but the fatigue is extreme and he has weakness and visible muscle wastage in his arms and legs. Does anyone have any tips please on how to counteract the fatigue? He is 47, first diagnosed August 2015.

Any help much appreciated.

Steroid taper

Hi all,

My dad is on the last leg of his steroid taper and is really struggling. Extreme fatigue and total loss of appetite as well being highly emotional. I think these are all common withdrawal symptoms but was wondering if anyone knows of anything that might help?

Dexamethasone - "Pseudo progression "

My husband commenced dexamethasone at 2mg in the 4th week of radiotherapy. He continued that for 2 weeks and then was weaned off. After 2 days off he had a partial seizure of one leg. He was re-commenced dexamethasone at 4mg. He has been on the 6mg for 4weeks. He has symptoms of being unbalanced and difficulty moving one leg so the dose has been increased to 8mg. Within hours he could walk better. How long to "too" long to be on this drug?

Dexamethasone

Please tell me why this is called the devil drug?

My friend is on 6mg a day now. What are the side effects that are troublesome? My friend that I'm caring for isn't able to express things due to the GBM so maybe stuff is happening that I don't know about?

Hydrocortisone VS Prednisone

My husband, diagnosed May 2015 with left frontal lobe GBM, had been using dexamethasone but the side-effect were becoming too severe even though he was down to 2mg per day. His arms easily bruised, bleeding from thinning skin. Does anyone here have any experience with Prednisone or hydrocortisone? Since Dec. 1, my husband started taking prednisone but he seems to get quite irritable even on 7.5mg. A friend, who happens to be a neuro-onc visiting from Scotland, recommended switching over to hydrocortisone.  Our UCLA neuro-onc recommends that we see an endocrinologist, but that's harder to find than you would think. Any conflicts with other off-labels meds or supplements? Thoughts?

Start DCA while on dex?

So, I have DCA in the freezer, ready to use.

Bought from PureDCA.com.

They recomended  600mg dca + 375mg of thiamin TWICE daily for 80kg man. My husband now is 84.6 kg.

Not sure if he can start DCA (sodium version) if he is on 7mg of dexamethasone and thus should have low sodium diet.

He currently does not have any treatment. 

Last DC vaccine was on 31st November 2016. 

SPMF treatment ended on 12th October. Were told that therapy 'lasts' for another three months (forgive me my imperfect English).

Current drugs:

Dexamethasone	4-3-0 (mg)
Omeprazole 20	0-0-0
Levetiracetam 750 mg	1-0-1
Endoxan 50 mg	1-0-0 (cyclophosphamide)
MGN-3 1000 mg	1-1-1 (shitake powder)
Rytmonorm SR 325 mg	1-0-1 (propafenonum for heart)

Supplements:

Vitamin D 5000 UI	0-1-0
Vitamin C 1000 mg	0-1-0
Caltrate Plus	0-0-2 (calcium)
Magne B6	1-0-1 (magnesium)
MarineOmega	1-0-1 (omega 3)
LifePak	1/2-0-1/2 (multivitamine)
Cordyceps	2-0-2
Reishi

We also plan to start applying 25% DMSO gel from Jacobs labs topically on his head.

(We hope to decrease his significant edema in the brain.)

Any advice on DCA start/not to start/when will be much appreciated.

Husband has all kinds of side effects from dex. Started higher doses on September. Moon face, insomnia, big abdomen, myopathy, osteopenia...

God bless,

Hana

Some Changes

Hello,

My dad is weaker today than he has been. The staff at the rehab facility put him in bed because he kept slumping forward in his chair and they were afraid he would fall out. He is also very tired.

We are working hard to get him CBD/THC in the hopes of boosting his appetite. I am also considering the Remeron that people suggested the other day. He eats very little, so I know that is a problem. The doctors are talking about increasing the steroid (he is at 2 mg. now). I really want him to be done with it because it is a double-edged sword, but is increasing it the best option right now? He has very little edema at this point. They are also talking about doing an MRI sooner rather than later. He has two sessions of radiation left.

Is the extreme weakness all part of the treatment? Is the tumor causing this? I am guessing it is a combination of things, and I want to help him. Meanwhile the doctors are making their suggestions and I am trying to figure out what is best.

I appreciate your thoughts.

Best,
Stephanie

Suggestions?

Hi,

My dad is due to finish up his first round of TMZ and radiation on Wednesday. Over the last few weeks he has declined considerably. The nausea and vomiting kicked in and he is very weak. His balance and mobility are limited at best. He has been in a rehab facility for a few weeks because he fell at home and ended up there. We tried to get him back home last week, but he is unable to perform basic functions on his own and/or with help from my mom. There will be people (including the rest of us) stopping in to help him once he gets home, but it will not be consistent, so the two of them need to be able to manage.

At this point he is not taking much in terms of supplements because the nausea and lack of appetite prevent him from putting much in his mouth. He is also eating very little and nothing healthy.

Once the chemo and radiation end and the steroid stops (he is at 2mg as of tomorrow), I want to give him whatever I can to build up his strength and breathe some life into him. Any suggestions?

I know it will not happen over night and that there is no magic pill, but I want him to come home. He desperately needs to be at home, and he needs to build up his strength for that.

Thanks,
Stephanie

New to GBM

Hi, my first post here so I hope I'm doing this right.  My husband was diagnosed with GBM on June 13th of this year...on the day my baby turned 8 months old.  One night when he was working late at home, he started having chills and feeling cold and started having a seizure in bed while we were sleeping.  He had 3 seizures that night and went to the ER and a mass was detected on his scans in his right parietal lobe.  He had surgery the very next day and the neurosurgeon said it was 99% removed.  At the time, they detected something else on the scans in his right temporal lobe...(I believe it was his first scan at the ER) that showed something, but they couldn't give us a definitive answer of what it was.  They said it could be swelling, but based on most recent scans, the NO said he thinks it's progression and that if it is, it's most likely inoperable and they will know for sure after chemoradiation is over.  I'm scared to death about the new find, although he suspects that it's not as aggressive as the one that was removed.  I'm not sure what he means by "progression" if it was there from the first scan and not as aggressive.  Wouldn't it be more appropriate to call it as another tumor rather than progression from his first tumor?  Am I not comprehending things correctly?  I ask this here as I am never able to accompany my husband to his appointments as I have my infant son and another 8 year old son and I don't have anyone to watch them.  I feel really helpless at times and focus whatever free time I have looking up what supplements and diets could possibly help him.  My research, however, is often not thorough as I am constantly interrupted by an unsleeping baby and an active 8 year old.  I'm hoping you wonderful members/contributors could help me out and take a look at the list of supplements I have compiled so far.... It's been a work in progress as my research evolves and I have taken out some, only to add others.

From what I can make out of his pathology report, my husband is MGMT unmethylated and IDH1 and IDH2 negative.  My SIL, who has been taking him to all his appointments, has sent in for Foundation One report so we are still waiting on that.

But this is what I have so far for my husband.  Please let me know if there is anything that is unnecessary as I feel bad that my husband has so many pills to take all throughout the day.  Also if there are any I should add and if my dosage should be increased, etc.  I would ever so appreciate it!  I was attempting to put him on a Ketogenic diet, but I'm too afraid to attempt as he has already lost some weight.  He went from 200lbs down to 185, which is still an average size, but he seems to have lost some muscle.  I am waiting for my Wokvel Boswellia extract to come so I can add that to his list as well.  If I add this, would it be safe to take out the Dex?  Right now I am putting him on a mostly organic diet with fresh veggies/soy/chicken and avoiding nuts because of Omega 6 and sugars and white starches.  I also wanted to add that my husband is going on week 4 of chemoradiation and has been getting good blood count results and has been able to work every day from morning till 4-5pm. Thank you so much if you are reading this!

Rx meds
Taken w/o food
Dexamethasone 20mg (1) 8AM
Famotidine 20mg (1) 8AM
Losartan 100mg   (1) 8AM
Levetiracetam 500mg (1) 8AM/ (1) 8PM
Zofran (1) 8PM
Temodar (2) 9PM




Supplements
Taken before a meal:
Berberine 500mg (1) 8AM/ (1) 5PM
Longvida Curcumin 500mg (2) 8AM/ (2) 5PM
Resveratrol 500mg (2) 5PM

Taken w/o food:
Life Extension Milk Thistle 750mg (1) 8PM
Melatonin 5mg (4) 9PM

Taken with food:
Red Reishi Mushroom 500mg (2) B (2) L (1) D
Fucoidan 310mg (5) B (5) L (6) D
Mushroom Science PSK/PSP 500mg (2) B (2) L (2) D
Mushroom Wisdom Maitake D Fraction Professional Strength (2) B (2) L (2) D
Green tea extract 750mg (1) B (1) L (1) D
Omega 3 Fish Oil 1100 mg (1) B (1) L (1) D

Life Extension Pteropure 50mg (1) B (1) L
Life Extension Soy 135mg (1) B (1) L
Vitamin D3 10,000IU (1) L
Life Extension Mega Lycopene 15mg (1)L
Probiotic 46mg (2) L
True Veda Ashwagandha 300mg (1) L

My husband - introduction

Dear all,

In August 2015, my husband (he is 35) had terrible headaches, his vision was affected,  then left side weakness. So went to emergency and two tumors were found. In frontal lobe 64x41x54mm and in basal ganglias 16x22x15mm. The bigger one was resected and the smaller one was inoperable. 

After month he had radiotherapy with concomitant temozolomide.

After around two weeks after the RT he got hydrocephalus. 

Was given shunt, then got meningitis, shunt was removed. Fortunately, now he does not need shunt.

Whole December in hospital, he was in the intensive care unit with meningitis reaching CRP 300.

He survived.

After that he started taking Valcyte. He is not taking any chemotherapy, because for MGMT unmethylated Temodar would not work much.

His biopsy is:  GBM grade 4, GFAP posit, Olig2 posit, IDH1 negat, IDH2 negat, p53 wild type, Ki67 25%, MGMT unmethylated, EGFR not mutated, KRAS not mutated.

Now briefly:

The smaller tumor got bigger and bigger and was operated 18.7.2016. It turned out to be mainly cyst (doctors surprised), with only really small areas shining (being active). Right now he has 32mg of dexamethasone just after the operation.

The leftovers from bigger tumor - got now very very aggressive, it is diffused, inoperable. And I think there is not much time now left.

My questions:

1. which supplements I can give him here in hospital while on high does dexamethasone?

2. which supplements, drugs would you advise to add to our protocol to which we want to return when he is at home again?

Prescribed drugs:

Valcyte

Keppra

Then he takes (will give precise mgs when at home):

ReishiMax Glp(Nuskin) - 3 times higher recommended dos

Cordymax  (Nuskin) - 3 times higher recommended dose

LifePak (Nuskin) - multivitamin

MarineOmega  (Nuskin) - recommended dose

Curcumin  (LifeExtension) - 3 times a day

Boswellia (300mg) - 3 times a day

Resveratrol 250mg (250mg trans-resveratrol, 100mg Quercetin) - 2 times a day

Melatonin - 5mg before bed (will increase this to 10mg)

Chlorela - 2x a day

Serapeptase -2 capsules early in the morning

Betaglukan

Vitwmin D - 5000 UI once a week

Rick Simpson protocol (should we stop it as we will start with DC vaccines?)

Banerji protocol (Ruta + Calcarea)

Carcinosin 200C

peptides (whole content not revealed) for immune system

peptides with reishi, cordyceps and more (not revealed to us)

Epiquercican (Dr Rath) - 3 capsules a day (lysin, prolin, arginin, EGCG, ..)

probiotics

meditation

avoiding sugar, restricting meat

Can we add milk thistle?

Can we add aloe vera?

We were in Lithuania more than month ago. DC vaccines are ready from my husbands blood (not from his tumor). Day before first DC vaccine he will have tetanus shot to increase the better outcome of DC vaccines.

We also started to cooperate with one scientist at the oncology institute, he now has samples from his tumor. He is expert on mesenchymal stems cells and vaccines and nanoparticles, so we hope to get to some state-of-the-art treatment too.

Any help will be much appreciated. 

Wishing you all lot of strength in fighting this beast.

Hana

Corticosteroids (eg dexamethasone) and survival in GBM

Click here to view abstract

This study includes such names as Roger Stupp and Michael Weller on the author list, so cannot be taken lightly.

This paper consists of a retrospective human study and a mouse study.  The mouse study shows an antagonistic effect of dexamethasone on the efficacy of radiation (mouse survival was shorter when given dexamethasone with radiation compared to radiation alone).   An anti-VEGF antibody (similar to Avastin) was used in another group mice as an alternative means of edema control, and no interference with radiation was observed.

"Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma."

Dexamethasone vs. confusion

My wife is very confused lately - more so than usual. It's been about two weeks after the SoC of radiation and chemotherapy.

We have been trying to wean her of Dexamethasone so she's currently on 4mg in the morning and 2mg at night. But we're worried that her state of confusion is dampening her already dampened spirits.

I'm very wary of dexa - at our first hospital, the surgeon gave her a whopping 64mg a day, or 16 tabs. Her tumor wasn't considered "a time bomb" at the time but two weeks later, we rushed her to the hosptial as the tumor became very, very aggressive. I don't have anything to support this but I'm certain that the dexa had a hand in this as I feel it increased the glucose in her blood resulting in the growth. Our NO says there's little support for this.

Now, our new issue is that she was fine on 4/4 so we dropped her (per the NO) to 4/2 but her confusion has increased dramatically.

I'm trying to counter this is 2400mg of Boswellia (specifically http://www.amazon.com/Boswellia-Serrata-1200-Mg-Capsules/dp/B00C6B17VM) as well as turmeric and celebrex but it doesn't seem to be cutting it.

Questions

1. Are my fears of dexa over-blown?
2. If they are not, what alternatives do I have to the dexa?

Thanks in advance!

Swelling

What is the best thing to use for swelling/oedema? My dad uses now 16 mg dexamethasone a day, and is feeling fine when he uses it. But they want to temper down the dosage so they gave him a couple days a go half of the dosage a day: so 8 mg. He didn't go react well on it , so now they increased the dosage. But i know he can not take dexa for life becaus of side effects etc. so i am searching for the best brand of boswellia or other things
Any suggestions?

New to GBM. 63 y/o Male. Here's my cocktail base plan. Thoughts?

Hi All -

First let me thank you for this board, for your posts and stories, and for your inspiration in a time of such devastation.  My father was diagnosed with a stage 4 GBM on Tuesday.  It's in his frontal left lobe and impairing speech and some basic memory, but nothing else.  Were getting second opinions on surgical options tomorrow and again hopefully Tuesday.  First NS said no.  I was in shock (diagnosis time) and didn't know enough questions to ask.

I now want him to take everything I can to help.  His vitals, heart, kidneys, liver etc are all excellent. He's very fit, non-smoker/drinker.  He is on board with whatever I suggest and will cooperate.  He is reading Ben William's book but cannot actively participate in boards like this as his brain is impaired. Typing and thinking of words is severely impacted.  My mother is a retired RN and will monitor blood pressure daily and blood glucose should we incorporate DCA or Metformin.  That said, two scientists in my extended family rejected my suggestions and instead pushed the 'clinical trial' route - which I believe benefits the greater good of mankind in the long term but does nothing for the subjects.  It's hard not to be discouraged by their emails of 'concern'.  I believe they would have a different opinion were it their loved one.  I've been following BW and Rich's doses from the cancer compass board as a starting point but unfortunately my background is in IT and not science.  Here's what I want to give dad.  Am I overlooking a drug/supplement that is crucial?  Unfortunately I don't know the MGMT status or IDH1 gene status.  I plan to ask tomorrow.  Any suggested edits?  So far he is tolerating everything I've thrown at him.

BETWEEN CHEMO SESSIONS:

- Accutane (13-cis-retin-acid), 160 mg/day, 14 days on, 7 days off    DON'T HAVE YET - How to get in US??

2 WEEKS BEFORE CHEMO:

- 220 mg Tamoxifen, 2 weeks before chemo.  DON'T HAVE YET

need aspirin daily and long walks for blood clotting

START WEEK BEFORE CHEMO:

- Verapamil, 600mg/day  Blocks extrusion pump mechanism at BBB increasing penetration of chemo (BCNU)

DAY OF CHEMO:

- Viagara  60 minute before (BBB helper)  Would this do the same thing as Verapamil?  Any conflicts?

CONTINUE DURING CHEMO:
- Verapamil, 600mg/day

CONSTANT (+ during chemo/radiation):

- Brewed Green Tea

- cannabis (TCH + CBD)

- Celebrex (Celecoxib), 200mg/day  (I want to up this to 600.  Will push our Dr)

- Chloroquine Phosphate, 250mg/day  (Dr said no, family member had a script)

- Coriolus versicolor extract PSK/PSP, 3g/day  DON'T HAVE YET - On the way via internet

- Curcumin/tumeric extract: 800mg/day

- Decadrone 2 mg day   (NS prescribed)

- Fermented Papaya Extract, 1000mg/day   DON'T HAVE YET

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

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

- Green Tea Extract, 4g per day

- Keppra  (NS prescribed.  Not sure dose)

- Maitake-D mushroom extract, 1200mg per day

- Melatonin, 20mg/day

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

- Omeprazole (NS prescribed, not sure dose)

- Reishi mushroom extract, 2.5g per day

- Resveratrol,  20mg per day

- Selenium, 200mcg per day

- Silibinin extract, 2g/day

- Soy Extract, 5g per day

- Standard multivitamin capsules, time-release

- Tagamet (cimetidine), 800mg/day

- Vitamin D 5000 mg a week (Dr said this was the max. I want to increase to 10,000 a day)

Thanks for any help or encouragement.  I'm incredibly grateful for all of you.

Annie

Tapering Decadron

This has been Chance's biggest challenge, it seems, so I wanted to ask for suggestions/support.

His resection was December 1, 2014, and he's been trying to divorce the decadron ever since. He is down to 1.75 mg per day: 1 mg at breakfast, .75 at lunch. It was suggested by Aunt Zelda's that he taper in quarters, instead of halves, and we liked the idea very much.

He's had a series of setbacks: a blood clot in his leg, bronchitis, his last round of chemo... He got very nauseated at the end of chemo and didn't eat for one full day, which means he didn't take his Decadron either, and he got a terrible, crippling headache. Yesterday, he ate a bit and he took the 1 mg Decadron and within a few hours he began to feel better. It gave us a peak into how much power the Decadron still holds.

His hematologist recently mentioned he has patients that are unable to get off Decadron, so they just continue indefinitely on the lowest possible dosage. Chance is 38 and his biggest complaint is insomnia, but of course he's gained weight and is discouraged every time he looks in the mirror. He has always been very physically active and worked out at least five days a week.

I recall Rich said he finally just bit the bullet and stopped, but I wondered what others had done. Chance is working, so a debilitating, endless headache is pretty much out of the question. Any ideas how long it may last?

BTW, Chance has just started Boswellia, which I know can help from an anti-inflammatory angle, but Dr. Lee (hematologist) said it will not help with the other symptoms.

Thanks.

Boswellia during radiation

Does anyone of you have experience with Boswellia serrata to replace the steroids during radiation??

i read a study with 4200mg /day ..what do u think??
Or should i go with 3600mg/day??

Sarah