Dear all,
What do you think about adding the above medications to the cocktail? I was browsing trials on MDA site and ran across this one
http://utm-ext01a.mdacc.tmc.edu/dept/prot/clinicaltrialswp.nsf/Index/2011-0374
Quoting:
I already take Metformin and TMZ. Have a chance to order Mefloquine and Memantine and wondering if I should. Is Mefloquine similar to Chloroquine?
Thank you!
What do you think about adding the above medications to the cocktail? I was browsing trials on MDA site and ran across this one
http://utm-ext01a.mdacc.tmc.edu/dept/prot/clinicaltrialswp.nsf/Index/2011-0374
Quoting:
Temozolomide is designed to kill cancer cells by damaging DNA (the genetic
material of cells). The damaged DNA may cause tumor cell death.
Memantine is designed to block the activity of a protein found on the surface
of cells that may control tumor growth and survival. This may stop further
spread of tumor cells.
Mefloquine is designed to block a protein that helps to clean the waste in the
cells and to destabilize the cell membrane. Blocking this protein may cause
tumor cell death.
Metformin is designed to block a protein in tumor cells that is important in
tumor growth and blood vessel development. This may cause cell death or reduce
the spread of the disease.
I already take Metformin and TMZ. Have a chance to order Mefloquine and Memantine and wondering if I should. Is Mefloquine similar to Chloroquine?
Thank you!
Personally, I would be cautious with mefloquine because of the potential for neurotoxicity.
ReplyDeletehttp://www.ncbi.nlm.nih.gov/pubmed/19174293
https://en.wikipedia.org/wiki/Mefloquine
There isn't much evidence yet to support its use other than in vitro.
Memantine is a glutamate receptor antagonist. There is some rodent evidence to support its use for gliomas, but it's probably mainly beneficial for tumors that are releasing large amounts of glutamate.
http://www.ncbi.nlm.nih.gov/pubmed/11533703
I'll add this study to the Drug Library.
But they give metformin 1000 mg by mouth twice a day for a 28 day cycle! Quite a high dose.
ReplyDeleteKatja, I´m currently taking 500mg tid of metformin
ReplyDeleteMore on mefloquine from the article "Chloroquine-induced autophagic vacuole accumulation and cell death in glioma cells is p53 independent" This is from 2010
ReplyDeleteCQ appears to trigger multiple death pathways in gliomas. However, its use in glioma patients may be limited by its poor BBB penetration. Therefore, we tested other lysosomotropic compounds for tumoricidal effects. Quinacrine and mefloquine were found to be much more potent than CQ in inducing GBM cell death in vitro. Both quinacrine and mefloquine have been shown to be effective in the treatment of cerebral malaria and have significantly better central nervous system penetration than CQ.34–36 Quinacrine has been reported to stabilize p53, induce the upregulation of downstream pro-apoptotic molecules, and induce p53-dependent tumor cell death.19 However, we report that quinacrine-induced death in gliomas is not incumbent upon an intact p53 gene. Moreover, similar to CQ, quinacrine induces dramatic AV accumulation and caspase activation suggesting a common underlying cellular mechanism of action. In summary, we found that CQ, mefloquine, and quinacrine induce cell death in gliomas that does not require an intact p53 gene and may be mediated by multiple death pathways.
Yes, it does seem to be more potent than chloroquine in vitro, but this probably means higher risk for neurotoxicity, which is what worries me.
ReplyDeleteThank you guys, I will hold off then, until they publish more results.
ReplyDeleteBtw, I take 850 mg of Metdormin twice daily.
I can't get hold of metformin so take Berberine instead
ReplyDeleteNicola, how much Berberine do you take a day?
DeleteHi Candy, I've been taking the Glycox 500 brand which includes 500 g berberine, I take twice a day after food. I'm in the UK and my Doc won't prescribe metformin
Deletehubby takes 500mg metformin tid
ReplyDeleteLinda, tid means three times a day? Thanks :)
ReplyDeleteYes..
Deleteqd = every day
bid = twice a day
tid = three times daily
qid = four times daily
Stephen, given the aforementioned article I cited, I wonder if mefloquine could be used on a rotational basis after active treatment has been completed. From the article, it appears there is anti GBM activity as a monotherapy (unless I missed something as I just scanned the article). So once CQ has been dropped from the cocktail at the completion of active treatment or whenever someone discontinues it, mefloquine could be added. Thoughts? Is there even enough research out there other than cited in this article to warrant considering this?
ReplyDeleteMike,
ReplyDeleteThe main thing to remember about this study is that it's in vitro. In the U87 GBM cell line, it took at least 8-10 uM (micromolar) to see any significant activity. It's very unlikely that much free drug would be found in the brain extracellular fluid, as the max plasma concentration in humans is ~3 uM, and only 2% of this is not bound to plasma proteins. At least rodent evidence can show that you can apply enough of a drug to inhibit tumor growth without killing the animal with side-effects from drug toxicity. In vitro, they can use as a high a concentration as they want to show an effect, without having to worry about side-effects or toxicity.
someone should evaluate fenofibrate,curcumin,cimetidine,metformin,fluoxetine,
ReplyDeletebetaglucan/vit C ,celebrex, and tadalafil in addition to standard therapy and ensure robust selenium and vit d levels--maybe combined with metronimic dosing of cyclophosphamide every 6 days and egcg, and maybe minocycline or mebendazole???--they are all referenced in the pubmed articles or in PMC