My 38 yo husband was diagnosed with GBM IV. He started with headache and after 12 hours he was paralysed on his left side. The tumor was in his right frontal lobe almost 5cm diameter. They have resected the main mass but it has infiltrated his coropus callosum on area of 1cm, which they say is unoperable. His tumor is IDH-1 wild type and methylated. Next week he is starting his chemo and radioteraphy. I am trying to educate myself between hospitals, work, child but it is too much for one person to handle. Doctors are refusing to use coctail aproach so here I am on my own on this path. I am so grateful to find this site and truly admire all of you for work and support.
This is what we have got so far but I will truly appreciate every tip or insight.
What is crucial at this point?
I am putting him on ketogenic diet.
He is taking
Metformin 500mg twice a day
Dekapote 500mg twice a day
Celebrex 200mg twice a day
Curcumin Longevida 2 capsules a day
Boswelia serrata 600 mg twice
Pterostilbene twice
alfa lipolic Acid once
Green tea extract twice
Broccoli sprout extract once
Reishi 1 caps Coriolus 3g Maitake 3g once
Melatonin 10mg once
Cannabis oil cbd
We have got chloroquine and disulfiram are they necessary now?
As for channel pomp inhibitors I was reading about them but still don't know if you are going for all them during chemo -like telmisartan, nexium, verapamil?
I am waiting for Cymetidine Tagamet - you are using it also during his radiochemotherapy? It is interacting with almost all drugs but I suppose I have nothing else antymigrating in his coctail.
I am a little confused with Keppra and risk of demethylation - if he is methylated is it necessary? If so when it is best to incorporate this?
What else should /could I do? Thank you and wish you all the best !
As we say to new group members, welcome to our group, but sorry you had to seek us out.
ReplyDeleteWas there any additional genetic info (EGFR amplification)?
Chloroquine: in the Mexican studies, chloroquine treatment was initiated prior to radiation and was continued daily throughout radiation and chemo at a dose of 150 mg/day chloroquine base (250 mg per day chloroquine phosphate). If you're going to use it, it's probably most effective combined with radiation and chemo. Also probably most effective in EGFR-driven tumors, according to some preclinical and retrospective clinical evidence.
Disulfiram could also work well with radiation, but there's been no trials of that combination (though I believe some people on this blog have used it during radiation).
Omeprazole and nexium (esomeprazole) are proton pump inhibitors. Telmisartan is an angiotensin-II receptor blocker. Verapamil is a calcium channel blocker that also blocks the P-glycoprotein drug efflux pump. They would all work in different ways. Verapamil has been used in cocktails with the intent of increasing exposure to other chemos (by blocking the drug extrusion pump at the blood-brain barrier, and potentially even in the tumor cells). There's little evidence (beyond in vitro) that it would work this way with temozolomide, but it may. It has increased the effectiveness of BCNU in animal studies.
Proton pump inhibitors are expected to both increase effectiveness of chemo, as well as disrupt tumor cells ability to regulate internal and external pH in their favor. My question about these drugs has always been: does enough of the drug cross the blood-brain barrier to make a difference in brain tumor therapy. There's little evidence to answer this question one way or the other.
There's some evidence that angiotensin-II receptor blockers (-sartans) could decrease edema in brain tumor patients and lessen the need for corticosteroids like dexamethasone. One study even found an association with better survival for brain tumor patients taking these drugs for hypertension. Some of these benefits could be independent of chemotherapy.
Cimetidine does have pharmacokinetic interactions with many other drugs, typically leading to higher plasma levels of other drugs (through decreased metabolism and clearance of the other drugs). These interactions tend to modest though, and do not necessarily cause problems. Metformin is one of the many drugs cimetidine interacts with (higher plasma levels of metformin when taken with cimetidine).
Keppra is not a demethylating agent. Animal and in vitro (but not human) studies show that it can decrease expression of the MGMT enzyme, and thus possibly sensitize MGMT unmethylated tumors to chemotherapy. The benefit might be less in MGMT-methylated tumors (in which the MGMT gene is silenced already by promoter methylation), but keep in mind that even in tumors considered to be "MGMT methylated" there may be cells or whole areas of the tumor where that is not the case. (MGMT methylation status can be heterogenous within tumors). To answer your question, if Keppra is beneficial in tumor therapy (beyond anti-seizure effects), it is probably most beneficial during monthly follow-up cycles of temozolomide.
Seems to me you're on the right track.
http://astrocytomaoptions.com/radiation/
Thank you for welcoming and your answer.
ReplyDeleteWe do not have EGFR status examined.
What do you think about this articles https://www.ncbi.nlm.nih.gov/pubmed/26786929
The more I am learning about GBM the more I am impressed and terryfied by it.
I wrote six paragraphs about this study in the 2016 edition of Ben Williams Treatment Options update found on virtualtrials.com:
Deletehttp://virtualtrials.com/pdf2016/benwilliamsTreatmentOptionsUpdate2016.pdf
In the table of contents go to chapter 6, then click on "Valproic acid/sodium valproate (Depakote)". The part about this study is under "Continuing Debate"
In this study, "use" of either valproic acid or levetiracetam/Keppra was defined as use at the baseline visit prior to radiation, or use at the first follow-up visit after radiation. As I wrote about Keppra:
"However, as one of the primary mechanisms proposed for a
survival benefit of levetiracetam is the inhibition of MGMT, it could be argued that sustained use of this drug during monthly adjuvant cycles of temozolomide is the time-frame of most concern, rather than time points immediately before or after chemoradiation."
The authors themselves have recognized the limitations of their study being: "lack of solid data on the dose and duration of valproic acid exposure".
Doses of valproic acid required for anti-tumor efficacy may be closer to the 25 mg/kg per day (in two divided doses) used in the phase 2 trial that had decent PFS outcome and very impressive overall survival outcome.
https://www.ncbi.nlm.nih.gov/pubmed/26194676
Typical anti-seizure doses may not be high enough, and as the authors of the Happold/Weller study acknowledge, the lack of information about dosing was one of the major limitations of their study.
The big issue here is that this large retrospective study was carried out in order to provide justification for a randomized phase 3 trial. Given their findings, such a trial may never be carried out.
My three cents...
ReplyDelete1. I would get help from either Aunt Zelda's or Green Health Consultants with the CO (cannabis oil) dosing. It can be modified to help him with symptoms and changing chemo protocols. After chatting with Eloise at GHC, I realized my life would have been a lot easier if I had gone to her from the very beginning. Also, ask permission to join https://www.facebook.com/groups/glioNOmore/ where you will get a lot of helpful hints on how to deal with the negative effects of CO.
2. I would add artemisinin and Leucozepin to your list of supplements. Dr. Zhang at Lifenhance (www.lifenhanceclinic.com) can help dose your husband with those. She is very kind but her English, although good, is a challenge on the phone so speak slowly and clearly. She REALLY knows her stuff.
3. If I had known about disulfiram, I would have taken it along with the Temozolomide from Day 1. I am MGMT promoter gene unmethylated and I would have tried anything that would have improved the uptake and retention of the chemo.
Best of luck to you as you figure this out.
Thank you all. Today he started his chemo and radiotheraphy. He managed to fast for about 30hours. I will try to keep him on keto diet with restricted calories (there are few trials recruiting patients with GBM). And my next questions are - is metformine still necessary? Second question is connected with DCA, which arrived today.I remember there is some interaction with DCA and chlorquine, so I am not sure if they can be taken together?
ReplyDeleteBest wishes for all.