Hi Stephen and everybody else.
I am trying to put together a cocktail for a low grade
glioma. I am sorry for my english and hope you can understand. Here is my history: Craniotomy on 19. 1. 2018
- 10% of the rather big tumor stays in head (right frontal lobe). Diffuses
Astrocytom WHO 2. IDH1 R123H positiv (IDH mutant), ATRX lost, MGMT methilated
at 14 %, 1p/19q not codelated. Photon radiation therapy 55Gy in progress. At
the time of radiation: Vimpat 250 mg/da, fish oil (from algae - EPA, DHA),
curcuma, ketogene diet.
After the end of radiation should I start the chemotherapy.
1) Does it matter how long time after radiation should I beginn? 2)Should I do
6 or 12 cycles – on what does it depend?
Here is my plan what to try:
CCNU + TMZ (following the CETEG protocol in a hope that it
gives me more time and decreases the risk of hypermutation)
Keppra 500mg 2/day (should I do up to 1000mg 2/day on chemodays?
Methadon (2x 35 dropps) and CBD+ THC (not sure here how
much) - I do not know if the combination is possible (would I be too high on
those drugs?)
Dissulfiram 500mg/day on chemodays together with copper
glutonate 3x 2mg/day. Should I take it as well on non chemo days and how much?
Melatonin 20mg/day before bed
Vitamin D alfacalcidol (no idea how much. I have very low
levels of vit. D recently)
Chloroquine 150 mg/day
viagra 20mg 2/day to open BBB
Selenium, zink and other supplements with minerals and
vitamins (because of the diat that is not optimal).
Fish (algae) oil EPA DHA
Berberine
Curcuma
Should I change the drugs/supplements on chemo/ nonchemo days - sometime more and sometime less
?
Should I try some other supplements and drugs or do I need
to leave something out? Any comment is apreciated.
Diet:standart veganish diet few days before chemodays to let
the cells proliferate on carbs so they can die in the process. Few days after
the chemodays when the drugs are out of the system back to ketodiet with low
methionin. This idea migt be a nonsence. What diet should I opt for at the time
of chemotherapy or it does not matter that much…?
Thank you for this great blog community and for your advice.
Vojtech (the Czech Rep. / Germany)
Because of your subtotal resection, you would have met the inclusion criteria for the RTOG 9802 trial, which showed a statistically significant improvement in both progression-free and overall survival with the addition of PCV chemotherapy to radiation for grade 2 IDH1 mutant astrocytomas such as yours.
ReplyDeletehttps://academic.oup.com/neuro-oncology/article-abstract/19/suppl_6/vi8/4590322?redirectedFrom=fulltext
With regard to the PCV protocol, it's debatable whether vincristine adds anything of value (due to poor blood-brain barrier crossing), and some studies show PC (procarbazine + lomustine) as having equivalent efficacy compared to PCV.
Procarbazine is a DNA-methylating agent that is metabolized to an active species presumed to be the methyldiazonium ion (the same active species that temozolomide is metabolized to). Temozolomide + lomustine or Procarbazine + lomustine (PC) would both be reasonable choices. The lomustine would work to counteract the tendency to aquire mismatch repair defects leading to hypermutation, a problem with single agent temozolomide and probably single agent procarbazine as well. Experimental evidence shows that cells with mismatch repair defects are *more* vulnerable to lomustine.
The standard time between the end of radiation and the start of monthly chemo cycles is about 4 weeks.
Patients in the RTOG 9802 trial received 6 cycles of PCV, but more could be given depending on the tolerability and blood counts. The CeTeG trial also provided for 6 cycles of TMZ alone or TMZ+lomustine. In some parts of the world 12 cycles of TMZ is more common.
Keppra is thought to be a chemosensitizer by having an effect on MGMT expression, although this might not make a difference for MGMT-methylated tumors.
Before starting methadone it could be a good idea to contact Claudia Friesen and also review the dose escalation protocol provided in this article:
https://www.ncbi.nlm.nih.gov/pubmed/28314286
"Patients usually started with stepwise
increase of D,L-methadone dosage over a period of 2-3 weeks.
Starting doses of 5 drops bid (5 mg daily dose) were increased
with 1-5 drops every 5 days (5 drops is equivalent to 2.5 mg)
according to the tolerance of the patients."
Drugs.com gives a moderate interaction warning for methadone + dronabinol (synthetic THC):
"MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients."
CBD is non-toxic even at higher doses, but THC dose is usually limited by the psychoactive effect a person can tolerate.
You could take disulfiram on non-chemo days as well, but I would drop the dose to 250 mg in that case. Even 250 mg daily could lead to peripheral neuropathy after a while, so you could also take breaks as some people do with DCA. Another option would be only doing the 500 mg daily on and a few days before/after chemotherapy days. Be very careful not to ingest anything with alcohol (ethanol) while taking disulfiram, including herbal tinctures, perillyl alcohol dissolved in ethanol etc.
I have mixed feelings about taking something like high dose vitamin D or alfacalcidol during chemotherapy. My theory is that Accutane (isotretinoin) interferes with chemo by causing fewer cells to be in a state of active division, and I'm wondering if alfacalcidol could do the same. However in the small clinical trial that was published alfacalcidol seemed to be effective when given during chemo or after chemotherapy was finished.
Redifferentiation therapy in brain tumors: long-lasting complete regression
of glioblastomas and an anaplastic astrocytoma under long term
1-alpha-hydroxycholecalciferol
https://www.ncbi.nlm.nih.gov/pubmed/11349882 [full text available in the Brain Tumor Library, folder 1]
The BBB effect of viagra is very time dependant and shorter than the interval that CCNU or TMZ are in the blood stream. Viagra is also affected a fair bit by having food in your stomach, with time to Cmax of 1 hr for 'fasted' vs 2 hr for'feed' states. So if taking, would probably make sense to do it with chemo, or even an hour after.
ReplyDeleteThe studies on Ketogenic diet with radiation look pretty promising. Lot less clear if doing it longterm is good. BUT, getting to high levels of ketosis IS HARD. Plan on spending a few weeks before RT to learn how to do it (getting blood meters, diets planned, time to get your body to adapt, etc). Also doing intermittent 1 or 2 day fasts during RT could make it easier to achieve (say sunday and RT monday).
High glucose at some point during chemo is probably not a great idea. Low grades are not dividing fast, nor starved for glucose, so unlikely you can spike cell division rates via temporary diet changes.