Relevant drugs/supplements/protocols for brain cancer:
- cusp9 protocol (Ref.)
- Chlorimipramine, the keto diet and Boswellic Acid
- Noscapine inhibits tumor growth in TMZ-resistant gliomas http://www.ncbi.nlm.nih.gov/pubmed/21925789
- Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas http://www.ncbi.nlm.nih.gov/pubmed/25542083
- Chloroquine enhances temozolomide cytotoxicity in malignant gliomas by blocking autophagy http://www.ncbi.nlm.nih.gov/pubmed/25434381
- Tetanus Vaccine Boosts Cancer Therapy http://www.nbcnews.com/health/cancer/tetanus-vaccine-boosts-cancer-therapy-n321596
- Asparagine depletion potentiates the cytotoxic effect of chemotherapy against brain tumors. http://www.ncbi.nlm.nih.gov/pubmed/24505127
- Antagonist drug Emend halts brain tumor growth http://www.news-medical.net/news/20130320/Antagonist-drug-Emend-halts-brain-tumor-growth.aspx
- Canadian researchers break blood-brain barrier with new ultrasound treatment http://www.ctvnews.ca/health/canadian-researchers-break-blood-brain-barrier-with-new-ultrasound-treatment-1.2648878
- Blood glutamate scavengers (Oxaloacetate) prolong the survival of rats and mice with brain-implanted gliomas. http://www.ncbi.nlm.nih.gov/pubmed/22297683 Glutamate transporters in the biology of malignant gliomas. http://www.ncbi.nlm.nih.gov/pubmed/24281762
- Complete response of a recurrent, multicentric malignant glioma in a patient treated with phenylbutyrate. http://www.ncbi.nlm.nih.gov/pubmed/12241121/
- ECCT http://www.
cancertreatmentsresearch.com/? p=865 - Dendritic Cells + NDV http://www.
cancertreatmentsresearch.com/? p=643 - POH https://www.cancertreatmentsresearch.com/?p=602
- Treating brain tumours with traditional Chinese medicine https://www.fau.eu/2016/02/02/news/research/treating-brain-tumours-with-traditional-chinese-medicine/ Identification of two novel Chlorotoxin derivatives CA4 and CTX-23 with chemotherapeutic and anti-angiogenic potential http://www.nature.com/articles/srep19799 (from venom of Chinese golden scorpion)
- Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice.
http://www.ncbi.nlm.nih.gov/pubmed/26106074
Eradication of experimental brain metastases of human non-small cell lung cancer by macitentan, a dual antagonist of the endothelin A and B receptor, combined with paclitaxel. http://meetinglibrary.asco.org/content/103362-127
N ote: One box containing Opsumit (macitentan) 10mg film coated tablets, 30 tablets per box. Price £2306.00 per box (Ref) Alternatively, it may be found in China (CAS 441798-33-0) - Pyrvinium Pamoate: targets CD133 in human glioblastoma brain tumor-initiating cells http://www.ncbi.nlm.nih.gov/pubmed/26152745
Pyrvinium pamoate – 5 mg/kg/day – (an Anthelmintic drug over the counter in countries like Sweden, Norway, etc.) - “Since IL-8 is clearly upregulated in glioblastoma and contributes to the fl orid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function.” https://www.researchgate.net/file.PostFileLoader.html?id=56b7358d5cd9e3cd3f8b457e&assetKey=AS%3A326467700445185%401454847373596
- Researchers have demonstrated for the first time that it is possible to inhibit the growth of brain tumors by treating the common Cytomegalovirus (CMV) https://www.sciencedaily.com/releases/2011/09/110927072612.htm
- celecoxib: Both glioblastomas and medulloblastomas express high levels of cyclooxygenase-2 (COX-2) that catalyzes conversion of arachidonic acid to prostaglandins and other eicosanoids with concomitant secretion of proinflammatory prostaglandin E2 (PGE2)[64–66]. In gliomas, the level of COX-2 expression is directly correlated to glioma grade and associated with shorter survival in glioblastoma patients[65]. Non-steroidal anti-inflammatory drugs, capable of inhibiting cyclooxygenase, significantly suppress the growth of glioblastoma and medulloblastoma in preclinical models[9,64,66]. Also, short-term use (< 10 years) of anti-inflammatory medication is associated with a protective effect against glioblastoma http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4308527/
- Prazosin https://www.sciencedaily.com/releases/2016/04/160421085706.htm
- Ribavirin
https://www.nature.com/articles/onc2016457
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783620/
http://europepmc.org/articles/PMC5814281/
Most of the above are accessible to anyone in terms of price and availability.
Based on my readings so far, it becomes apparent that intracellular Cl modulation is a way to target GMB. Drugs or supplements that can modulate Cl channels are:
- Metformin – Metformin impairs the chloride current directly interacting with the extracellular portion of CLIC1 (chloride intracellular channel 1 – a transiently active channel essential for GBM growth). Reference: Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5b%5d=2617
Indeed, here is a scientific article showing good potential of Metformin against GBM and even more when combined with DCA or TMZ https://www.omicsonline.org/individualizing-chemotherapy-using-the-antidiabetic-drug-metformin-as-an-adjuvant-1948-5956.1000197.pdf - Scorpion venom
- Lansoprazole and possibly Omeprazole seem to also inhibit chloride channels http://www.ncbi.nlm.nih.gov/pubmed/10711360
Other relevant references:
- Treatment Options for Glioblastoma and other Gliomas http://virtualtrials.com/williamsTreatmentOptions2015.pdf
Disclaimer:
This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.
It is a comprehensive list, but I would add Macitentan to it, paper:
Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice.
http://www.ncbi.nlm.nih.gov/pubmed/26106074
Macitentan inhibits pathways linked to proliferation, angiogenesis, invasion, metastasis and chemoresistance.
Thanks for the helpful comment Ovidiu. Macitentan is a new one to me and it seems to be relevant to other cancers as well.
Dear Daniel,
How are you?
With relation to the possible use of macitentan for GBM that you mentioned in this thread (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4780217 from Oct 2015), which I also saw @ovidiu mentioned in the drug cocktail (COC protocol) thread,
I AM REALLY THRILLED with these amazing results! I don’t think I saw another case (even in lab with mice) of a complete GBM remission and we sure all wish it could be reproduced!
Then, I managed to find 2 clinical trials with macitentan + TMZ for cancer (GBM):
a) https://clinicaltrials.gov/ct2/show/NCT01499251 / Jan 2012 for 1 year – phase 1/1b trial: macitentan+TMZ for recurrent GBM [75 patients] – Results: “Terminated (Results did not clearly support continuing development in recurrent GBM)”
b) https://clinicaltrials.gov/ct2/show/NCT02254954 / Jan 2015 for 3 years- phase 1 trial: macitentan+TMZ for newly diagnosed GBM or gliosarcoma [ 30 patients] – Results: “Terminated (Sponsor decision due to low recruitment)”
I must say that considering the amazing results in vivo with mice from 2015, I became a bit confused/ suspicious about these technical/ unclear terminations of the 2 clinical trials…
1. In case you have any idea or additional info about the results of the 1st trial from 2012 (or other trial I might have missed) we will be happy to hear about it.
2. in the trial with mice, the macitentan dosage was 10mg/ KG/ day.
So, if we want to reproduce this with a patient, should he take also 10mg/ kg/ day? remark – I saw the documentation of this drug states 10mg/ day as the maximal dosage for treating PAH (pulmonary arterial hypertension) and the 2 above trials set 150mg and up to 375mg macitentan.
Many thanks!
Best wishes!
Nissim
HI Nissim,
Next to the info from Johan, on this page https://www.cancertreatmentsresearch.com/links/ (in the drug related section) I shared a file that is often used in the labs to make the conversion. Conversion of mice to man requires to apply a 1/12 factor. That would lead to 0.833mg/kg/day for humans. That would be about 60mg/day for a 70kg person. In the clinical trial they probably pushed the dose as high as possible while being safe.
Kind regards,
Daniel
Hi Nissim, this should help with the conversion:
“simple practice guide for dose conversion between animals and human”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/
Thanks a lot Johan! I did not had this one. I will add it on the links page.
Hi Nissim!
I was studying a good time macitentan for gbm, in fact I was about to acquire it but the results of the clinical trials you mentioned disappointed me.
I have followed the use in several patients and chose not to use it for my mother. It is possible that within a “cocktail” therapy is more effective but I had to opt for other molecules.
In this brain tumor blog you will find several discussions about macitentan:
https://btcocktails.blogspot.com/2015/08/macitentan-opsumit_1.html
My best wishes!
Dear Danial and all,
I hope you are all OK and successful with your treatments and help
My brother is using Novocure TTF (Tumor Treating Fields) device for the last few months as one of the treatments for GBM.
A few days ago we got a link to an interesting lab study results from 2017, named “Synergistic Inhibition of Glioma Cell Proliferation by Withaferin A and Tumor Treating Fields” – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711586
Remark – I understand that Withaferin A is made from “ashwagandha tree”
In this study they used Withaferin A with TTF and found that this combination significantly inhibited the growth of the glioma cells to a degree beyond that of Withaferin A or TTF treatment alone.
Remark – They also refered to an earlier study where Withaferin A was shown to inhibit the growth of several glioma lines at an IC50 of 250 nM – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597337
In the study they tested several concentrations of Withaferin A (0 to 0.3 μM) combined with TTF and found out that concentration of 0.1 μM or above gave the same improvement (at 0 μM there was no improvement).
Q – My question is regarding the transformation calculation of the Withaferin A concentration used with cell lines in lab (0.1 μM) to human dosage. What should be considered for this?
Any help will be appreciated!
Thank you as always!
Beat regards,
Nissim
Hi Nissim,
Great to hear that your brother has access to Novocure!
Regarding your question, here is my view: Converting Withaferin-A concentrations used on cells to humans is challenging. The best is to search for trials on humans using Withaferin-A and use what came out of those studies as safe. Here is an example of a phase I trial https://www.sciencedirect.com/science/article/pii/S0975947618307897
Kind regards,
Daniel
Thanks a lot Daniel for the general concept and the specific link to this trial summary!
Best regards,
Nissim
Hi Daniel and everyone!
How are you doing? I sure hope you are all ok and health situation is improving!
I happened to find this study about the possible use of relatively old antihistamine, named clemastine (Tavegil) to fight and kill invasive glioblastoma cells.
https://www.embopress.org/doi/10.15252/emmm.201809034
Brief summary:
This study mention the fact that invasive gbm cells are chemoresistant, impossible to remove by surgery, and cause tumour relapses.
Also, the heart‐specific, fatty‐acid binding protein 3 (MDGI/FABP3), was highly expressed in mesenchymal glioblastomas, and its high expression correlated with poor patient survival.
Yet, this study identified the vulnerability of invasive glioblastomas for lysosomal leakiness, regulated by MDGI/FABP3, and induced in vitro and in vivo by cationic amphiphilic drugs (CAD).
LMP (lysosomal membrane permeabilisation) inducement by some drugs (for example by clemastine) cause to MDGI silencing, which in turn dramatically compromised the viability of patient‐derived glioblastoma cells in vitro and impaired neoplastic initiation in vivo, while its overexpression promoted tumour invasiveness.
MDGI silencing led to progressive depletion of intracellular phospholipids essential to the integrity of lysosomal membranes, which induced caspase‐independent glioma cell death via LMP.
Thus using clemastine might kill invasive gbm cells.
As much as I understood, clemastine is an over the counter drug in USA.
I also found several threads about the possible benefit of using clemastine for the treatment of multiple sclerosis (MS).
Did anyone heard of its possible use?
Any remarks on this study are appreciated.
Many thanks and best wishes!
Nissim
Hi,
I find it important to add this short but perhaps simpler article, reporting on the above mentioned study:
“Achilles Heel” of Glioblastoma Found?”
https://www.nfcr.org/blog/achilles-heel-of-glioblastoma-found/
Let us hope it is indeed an Achilles Heel of this disease!!!
Regards, Nissim
Hi everyone,
After also getting additional information from the Prof’ who managed this study,
we got also a reference of a trial that used clemastine for MS (Multiple Sclerosis). in this study the participants got 5.36 mg clemastine fumarate (as I understood it is eq’ to 4 mg clemastine) x 2 / day, for 90 days with no special side effects, except for drowsiness, which is the major common side effect when using clemastine.
We managed to find an online pharmacy in the UK that we can buy clemastine (Tavegyl) and when we’ll get it we’ll have to see how to incorporate it into the current protocol, while hoping for minimum or no drowsiness.
Any further comments/ remarks are appreciated!
Health and a happy new year to you all!
Best wishes,
Nissim