Friday, 29 December 2017

Our cocktail and treatment tactics: CCNU+TMZ (CeTeG) + CUSP9v4


Today my mother had the last day of radiation therapy+TMZ.
(Diagnosis: Glioblastoma, MGMT methylated)

1. We plan to wait 2-3 weeks before the increase in the platelet count (now 142) and start with
CCNU+TMZ cycles (as in CeTeG trial).
Also, at the same time we want to start CUSP9v4 protocol .

But in CUSP9v4 protocol TMZ is taken daily in small doses.
I do not know how to take TMZ better. As in CUSP9v4 protocol, or as in CeTeG protocol (CCNU+TMZ)? What can you recommend?

If we take TMZ, as in CeTeG trial, we want to do intravenous injections of curcumin
every day of taking TMZ (5 days in 6 weeks).

2. Also we increased the dose very slowly, and now we take it every day:

DCA - 2x1300mg (2 x 20mg/kg/day)
Metformin - 2x1000mg
Alfacalcidol - 2,5mkg
Delagil (Chloroquine) - 1x250mg
Valdoxan (Agomelatinum) - 50mg (in the bed) (Cancel when moving to Sertraline from CUSP9v4).
Extra virgin olive oil, 1 tablespoon (on an empty stomach)
CurcuBrain, Longvida Optimized Curcumin (Now Foods) - 5х400mg
Aronia (Eclectic Institute) - 1x450 mg
TransmaxTR, Trans-Resveratrol (Biotivia) - 4x500mg
pTeroPure, Pterostilbene (Life Extension) - 4x50mg
Berberine (Thorne Research)- 3x500mg
Shark Liver Oil (Norwegian Fish Oil) - 3x689mg
Max DHA (Jarrow Formulas) - 2x484mg
Silymarin, Milk Thistle Extract with Artichoke & Dandelion (Now Foods) - 1x300mg
EGCg, Green Tea Extract (Now Foods) - 1x400 mg
Brocco Max DR (Jarrow Formulas) - 3x30mg
Boswellia Extract (Now Foods) - 2x250 mg
Ashwagandha Ghan Vati - 2caps
Oxaloacetate, OAA (Fractal Health) - 1x250mg
Mito-Charger (Advanced Orthomolecular Research AOR) - 3caps
Selenium (Now Foods) - 1x100 mcg
I also ordered and waiting for the delivery of PSK/PSP.
Tomato juice 1-2 cups
Young shoots Broccoli
Adding aronia (chokeberry) to the tea
I think we drink a lot of food supplements, but so far there have been no side effects and I do not know what to cancel!(

3. I also with great difficulty have already ordered perillyl alcohol, and now I am studying all the instructions for treatment with it.

4. We also want to try Nivolumab. The doctor assured us that we will be able to monitor the side effects by abolishing or decreasing the dose. Our doctor suggests starting with a dose of 100 mg / 2 weeks and then increasing 200 mg / 2 weeks. I'm not yet sure about Nivolumab, since we had a large remaining tumor after the operation(((

5. Next, I want to do a test for the amplification or overexpression of the EGFR gene.
In this case, we will cancel CUSP9v4 protocol and I want to consider pulsed lapatinib (or an analogue), as in this study: (I can not yet understand what kind of research was done to select niacinamide? What kind of research should I order?)

Unfortunately we did not have any tumor samples left. We signed a paper that we give samples of the tumor to the clinic where the mother was operated (University Clinic of Frankfurt on Main).
If we do not give back the remnants of the tumor, I will look for testing EGRF on the model of blood. I'm not sure that this is possible.

Stephen wrote that maybe this test will tell me about the overexpression of EGRF and maybe I'll order it:

6. I want to do a test here for the effectiveness of DCA for my mother and decide whether to take it further or cancel it:
I do not know what exactly is being investigated in this test. Maybe someone knows? I would then have ordered this study somewhere else.

7. I do not quite understand the results of our immunohistochemical study. Maybe there is something special about this data?
IDH-wild type,
IDH: IDH1 (R132H) negative (IHC),
ATRX: Preservation of nuclear expression (IHC)
H3.3: No evidence of K27M mutation (IHC)
P53: no accumulation of p53 (IHC)

P.S. I would like to write about my admiration and my great gratitude to Stephen, for devoting himself to helping other people fighting this deadly disease.

1 comment:

  1. The CUSP9 protocols were written for recurrent GBM in mind, that is, in patients that have already recurred following the standard 5 day TMZ schedule.

    The selection of niacinamide in that study was based on "morphoproteomic" analysis, or identification of proteins in the tumor cells, their state of activation and location within the cell. I've not heard of any commercial services offering complete morphoproteomic analysis in the same way there are commercial services offering comprehensive genetic sequencing.

    The english translation of the German webpage on DCA says "whether a fermentative metabolism is present in our patients, we see by special individual blood tests before treatment". In most GBMs, there is "fermentative metabolism" happening, that is the conversion of pyruvate to lactic acid, even in the presence of oxygen, otherwise known as "the Warburg effect". This would not provide any clue as to proper dosing of DCA for your mother. As explained on the Drug Dosing page on this blog: "DCA dosing is tricky, as there is a wide interpatient variability in DCA metabolism, with some patients being slow and others being fast metabolizers. This difference is mainly mediated by variations in the GSTZ1 gene, which encodes for an enzyme involved in DCA metabolism." Genetic testing of the GSTZ1 gene (from a blood sample) could predict whether a higher or lower dose of DCA is required, but most people rely on trial and error to figure out the dosing of DCA (lowering the dose if peripheral neuropathy or other dose-limiting side-effects appear).

    The IDH1, ATRX, H3.3 results don't tell you very much except that it isn't IDH1 or H3.3 mutant. It's hard to say what "no accumulation of p53" actually means. It could mean that the TP53 gene is not mutated, because high levels of p53 protein accumulation is often a sign of mutation. On the other hand some gliomas have frameshift mutations in the TP53 gene, which can also lead to absence of p53 detected by IHC tests.

    The EGFR testing (either for EGFR gene amplification or EGFR protein overexpression) is the most likely target for targeted therapy in GBM. I don't understand why that isn't a standard test for every newly diagnosed GBM.