Tuesday, 4 December 2018


Hello Stephen and all,

We have finally received the MGMT status of my aunt's tumour, it is methylated. Now waiting on EGFR amplification, which Princess Margaret in Toronto said they would test for as part of her participation in the marizomib clinical trial.

Grade IV Glioblastoma
  • idh(-) wildtype, ATRX(+), GFAP(+), p53(+)
  • The ki67 proliferation status is estimated at 10%
  • MGMT status: Methylated
I tried to come up with what I think is a list of the drugs with the most potential to put in a cocktail for my aunt. I do not want to overwhelm her with tons of prescription pills…so trying to keep it on the smaller side right now. I also do not know how much difficulty we will have in obtaining the prescriptions (mainly chloroquine given its use primarily with Malaria).

She is already taking:
Imipramine 25mg – should we consider switching this to Chlorimipramine?
Atenol 50mg
Hydrochlorothiazide 25mg
Apo-Phenytoin 300mg – this is her anti-seizure med
Co-Ranitidine 150mg
PMS-Dexamethasone 4mg
Not sure if any of these have any benefits in cancer treatment, perhaps Imipramine?
Wondering if we should ask to switch to Keppra or Depatoke for anti-seizure?

She will be starting a Ketogenic diet today, and her treatment of concurrent TMZ and Radiation will begin in about a week once we find out if she will receive Marizomib as part of the trial.

Is there anything you would suggest I add or remove?
I am still looking into the dosage of cannabis oils.


Drug
Dosage


Valproic Acid (Depatoke)??
OR
Levetiracetam
(Keppra)
1000mg
Chloroquine
250mg daily
Cimetidine (Tagamet)
800mg daily
Celebrex
200-400mg daily
Fluoxetine (Prozac)

Not sure if this would be helpful since she is methylated?
40mg daily
Metformin
500mg
Chlorimipramine
25mg daily escalated to 150mg daily


Supplement
Dosage


Boswellia (Wokvel Brand)
500-1000mg
Green Tea or Extract
700 mg 40% EGCG
Curcumin (Longvida) (AOR Brand)
2000mg +
Berberine
500-100mg daily (divided doses)
Melatonin
10-20mg
Omega 3 Fish Oil
TBD
Probiotic
TBD
Vitamin D3
5000-10,000 UI
Maitake D-Fraction
(mushroom)
100mg
Reishi mushroom extract
1g  per day
Turkey Tail - ie PSK
(mushroom)
3000mg
milk thistle
1000-2000mg
CBD / THC
200 mg THC
200 mg CBD
50 mg THCa



Thanks for your help,
Palma
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9 comments:

  1. Jo Jo4 December 2018 at 15:28

    As far as Clomipramine is concerned, 200mg/day maybe needed to reach an anti-tumour effect.
    Please check the combination of Boswellic Acid/Clomipramine. I don't think they can be taken together.

    ReplyDelete
  2. shares5 December 2018 at 03:23

    Yes it is either Boswellia or Clomipramine at 200mg/day. Clomipramine will make you very sleepy, at least it did me. Boswellia would be so much better but you need to take very large quantities and as it is not made by a pharma, you probably will not know what's in it, most likely a lot of fillers. I once bought boswellia powder from India bulk (1kg bags), it came with certificates etc, I occasionally made capsules with it, it is extremely sticky and difficult to handle. Boswellia trials use large doses 8000mg/day if I recall correctly.


    You said your aunt's tumour is methylated, but do you know the actual % ?

    ReplyDelete
    Replies
    1. Unknown6 December 2018 at 07:53

      Thank you, I have tried to source the best quality/brand through my cousin who is a Hollistic nutritionist - Genestra through Seroyal. But you are right, that there still may be alot of fillers.

      The report was printed out but the office was running out of ink and unfortunately I cannot see it very well. I looks like all it says is:

      MGMT Promoter methylation was detected.
      methylation-specific multiplex ligation-dependent probe amplification (ms-mlpa)

      Nothing about a % of methylation. Why do you ask? Should I ask for this? How can it help?

      Thanks!!

      Delete
    2. shares6 December 2018 at 08:15

      I had two methylation tests and in both cases hypermethylation was expressed as a percentage. "MS-MLPA … … showed moderate hypermethylation (mean ratio 0.56)"

      Delete
    3. Stephen W6 December 2018 at 09:52

      You both might be interested in this study that just came out.

      https://www.ncbi.nlm.nih.gov/pubmed/30514777
      MGMT Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide. A Pooled Analysis of Four Clinical Trials.

      It's saying that a higher degree of methylation doesn't lead to better outcomes in methylated cases, and that "grey zone" methylation cases still get significant benefit with TMZ. This study was authored by some big names (Hegi, Stupp, Gilbert, Weller etc.)

      Delete
  3. Stephen W5 December 2018 at 11:04

    Click on "clomipramine" label from the menu of labels to see prior discussions, Especially
    http://btcocktails.blogspot.com/2016/10/pilkington-interview-on-clomipramine.html

    So on the one hand we have some observational evidence (but not formal clinical trial evidence) that clomipramine could be helpful, but not even that level of evidence for imipramine (though they're in the same class of drug).

    Drugs.com mentions a potential for a major interaction between a tricyclic antidepressant such as imipramine and a SSRI such as fluoxetine: "GENERALLY AVOID: Coadministration with fluoxetine may significantly increase the plasma concentrations of some tricyclic antidepressants (TCAs). The proposed mechanism is fluoxetine inhibition of CYP450 2D6, the isoenzyme responsible for the metabolic clearance of many antidepressant and psychotropic drugs. Seizures and delirium have been reported, as well as a fatality attributed to fluoxetine-induced chronic amitriptyline toxicity. Pharmacodynamically, the combination of fluoxetine (or any other selective serotonin reuptake inhibitor) and a TCA may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5HT1A receptors." So I would avoid such a combination unless your aunt could be monitored frequently for early signs of serotonin syndrome etc.

    They've had good clinical trial outcomes in adding Depakote during the 6 weeks of chemoradiation, see my review of that trial here:
    http://astrocytomaoptions.com/radiation/
    However the dose of Depakote used in that trial was higher than the typical anti-seizure dose.

    Ranitidine is the same class of drug as cimetidine. There have also been positive studies of famotidine in breast cancer, in terms of immune effects.
    https://www.ncbi.nlm.nih.gov/pubmed/16391436

    ReplyDelete
    Replies
    1. Unknown6 December 2018 at 08:29

      Thank you Stephen, I will definitely check on all the drug interactions. I realize that she should probably only be on one anti-depressant at a time - so it would mean switching over from Imipramine to Prozac.

      Already got some resistance about switching from the current anti-seizure drug, as Oncologist said "they are all good drugs, and the one she is on is fine".
      Will be consulting with our long time family doctor for other prescriptions from now on. Just trying to present him with something well thought out and researched.

      Will ask about switching from Ranitidine to Cimetidine, as drug seems to do the same job, but cimetidine seems like it has more benefit to GBM - so seems reasonable Doc will agree.

      https://academic.oup.com/nop/article/3/3/154/1751853
      "A large proportion of GBM patients require antacid treatment, commonly due to corticosteroid side effects—providing another rationale for use of H2 blockers. With respect to incorporating cimetidine vs ranitidine, it is unknown whether one would have a more pronounced effect on the immune system. Cimetidine may also have other actions against glioblastoma."

      Thanks for your help.

      Palma

      Delete
    2. Stephen W8 December 2018 at 11:31

      "they are all good drugs, and the one she is on is fine".
      This might be true insofar as seizure prevention goes, but the intention of switching to valproic acid was for the anti-tumor effects in combination with radiation, as per this phase 2 clinical trial (perhaps you could direct him to this paper)
      https://www.ncbi.nlm.nih.gov/pubmed/26194676

      We don't have any clinical evidence of cimetidine for GBM. There has been a mouse study, but none of the other H2 antagonists were tested for GBM, and moreover the mouse study was done in nude (immunodeficient) mice, so any positive effects of cimetidine on immune response would not be seen in such a model. Cimetidine may be better than the other H2 antagonists, but we don't know this for sure. The evidence is too limited/

      Delete

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