Hi Manuel,

Thank you so much for taking the time to write this comment. I understand how difficult it is as you have so much to take care of, including taking care of your dear mom and working full time as the same time. So please use your time for that instead of spending time discussing on this website. What i only ask from you and others with whom I communicate by e-mail is that when there are general questions (not personal), please ask them on this website from time to time so that others can benefit from the related discussion. This is because lately I spend most of my time answering e-mails and calls, and as a result I have no more time to reflect the learnings here on the website so that others benefit.

I would also like to add again that all the ideas and knowledge I share with you or others (including that going through private communications) goes with the Disclaimer on this website. Everyone has to use that as input only while discussing with their medical doctor the best approach in line with patient’s status, and should not replace the medical advice.

Beyond that, I am happy to hear about the fact that your mom is doing better and she is now in a stable situation since you implemented approaches to support chemo, which as I understood was not anymore effective prior to that. I very much think 2DG metronomic plays a major role in that outcome.
Indeed, I think Taurolidine is a treatment approach that is relevant for glioblastoma, but it requires an intensive treatment.
Increasing slightly the frequency of 2DG metro may be an easier approach that could help.

Kind regards,
Daniel

Hi Daniel.

I believe that you were wrong which has written the protocol is Manuel my friend,is the protocol of his mother.

kind regards.Marcos

HI Marcos,

sorry for writing your name while responding to Manuel.

I did had Manuel in my mind as I was speaking with him on the e-mail too, but just wrote your name instead. Sorry for that. I'l change it now.

Kind regards,
Daniel

HI Manuel,

The priority for me would be to build a coherent strategy. So that even if there are drugs that may be very relevant, if we really need to take out some in order to add more along the strategy, I would take out those that are not part of the specific strategy.

In my view, one of the essential strategy in GMB is related to the fact that GMB is known to be very glycolitic. This is why I would build the strategy such that will address that aspect as good as possible. Having this in mind, here is how I think:

– Metfomin – has high priority as a part of the metabolic approach and pH approach (even if it is increasing glycolisisi it will decrease blood glucose levels and will address the cancer cells relying on respiration – using Metformin, means we also need to make sure we add glyco inhibitors)
– QUETIAPINE is a good one but we can remove if we need to make place for another better drug – therefore, this drug has medium priority
– Ezitimibe – medium priority as it is part of the cholesterol approach (which is good but this is another strategy)
– Statin – medium to high priority as it is part of the metabolic, pH and cholesterol approach
– NAPROXEN or CELEBREX – high priority due to anti inflammation action that is important specifically for brain c patients
– Mebendazole/Fenbendazole – high priority but would use only one of them instead of two at the same time (e.g. one week one and the other week another one) to make space for more drugs
– SODIUM PHENYLBUTIRATE – high priority due to relevance to brain c patients (is may act like DCA)
– Thalidomide – medium priority (although good for anti angiogenesis effect)
– Tamoxifen – high priority (multiple actions)
– Aspirin low dose – high priority (anti inflamation)
– CANAGLIFLOZIN – high priority (anti glycolisis)
– Supplements you use are very good in my view

Therefore, based on the list above you could remove QUETIAPINE, Ezitimibe, Thalidomide. That doesn’t mean they are not good, it’s just making choices given the limitations. We could always start them again at a latter point.

By removing those, I would make space to introduce:
– Acetozolamoide or TOPIRAMATE to address CA IX (pH strategy)
– Stiripentol which is a LDH inhibitor (metabolic strategy)  https://www.cancertreatmentsresearch.com/a-list-of-mitochondria-inhibitors/#comment-7986
– Syrosingopine would be great to inhibit MCTs but this is difficult to find  https://www.ncbi.nlm.nih.gov/pubmed/30540938

Of course, if we feel that things are going right as used now, I would not change anything.

But it’s important that we keep in mind the profile of GMB as highly glycolitic and the fact that we now know and have tools to influence that. I like cholesterol strategy a lot but I think its important to be stronger on the metabolic line, that is why some of the drugs from the list above and part of the cholesterol strategy have lower priority – it’s all about the context and limitation of nr of drugs we can use.
From a metabolic point of view, the drugs in the list above are doing the following:

– Metformin (mito activity lowering and blood glucose lowering),
– Statin (MCT lowering).
– Aspirin (MCT lowering),
– Mebendazole/Fenbendazole (GLUT1 lowering)
– Sodium Phenylbutyrate (activate mito if not the case)
– Tamoxifen (fibroblast lowering if any in brain c – they are suppliers for fuel)
– Canaglifozin (glucose transport lowering)
– Omega 3 may lower Na/H exchange

If glycolisis is still active, Acetozolamoide will help to acidify the cell when using glyco so it can be killed.  https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/
And Stiripentol will try to stop glycolisis somewhere at a downstream level.

Tranilast, I like it a lot but maybe Tamoxifen is enough to address fibroblast (in brain c the existence of fibroblasts is a little debate, in literature).

Manuel, I hope the above helps!

@daniel

Hello friends!

I will be updating changes in cocktail therapy in this section.
Exactly two years have passed since the last multifocal recurrence of my mother's brain tumor. Several opinions gave a maximum life survival of 6 months ... they are already 24 months and in some things improving. In August of this 2020 we will turn 5 years of diagnosis and thanks to all the help of this magnificent blog we will continue the fight without a doubt!
The current cocktail looks like this:
  -tamoxifen 80 mg / d (some breaks to avoid
  thrombi and problems with QT interval along with other drugs)
 - metformin 1700 mg / d (except on days of vitamin c iv)
- Canagliflozin 100-200mg (alternated with metformin, far
  from 2DG)
- pitavastatin 2 -4 mg in cycles with weekly breaks
- sodium phenylbutyrate 4- 5 g daily
- celecoxib / diclofenac (400mg / 100mg) the alternate one
  week inside another week outside
- doxycycline 200mg (together with vitamin c iv and salinomycin iv)
- silybinin / silymarin 2000mg (except on vitamin c days)
- dha 2500 mg / d
- sodium butyrate 600 mg / d
- magnesium gluconate 1500mg / d
- HCA 1500 mg / d
- mitohonokiol 5 mg / d (with breaks)
- Liposomal quercetin 60 ml (1500mg of active substance
  except days of vitamin c iv)
- aspirin in very low dose (distanced from AINES and
  especially hydroxychloroquine)
- hydroxychloroquine 200mg (especially together with
  salinomycin iv)
- 250-500 acetozolamide (only a few days, I am not sure if
  my mother tolerates well)
- salinomycin iv once a week (combined with doxycycline
  200mg, metformin 1700mg, hydroxychloroquine 200mg and
  Canagliflozin 100mg)
- vitamin c iv 2-3 times a week (combined with doxycycline
  200mg
(I avoid drug interactions so I alternating some and distancing others).
I have given rest to fenbendazole and metronomic 2 DG.

After weeks of reflection I have decided to introduce TAUROLIDINE iv. Our economy will suffer greatly but I think it is an option that I must try.
I was concerned about studies in rodents that showed liver toxicity but I have not seen any of this in the data published in humans and as always, they are risks that we must take.
Of the options Daniel shares in his great summary on taurolidine, I think using 2 bottles of 250 ml a day 2 days a week is a good option. This calendar option would also allow me to look for taurolidine synergies the rest of the days and use other iv weekly. https://www.cancertreatmentsresearch.com/taurolidine/
Daniel recommends the concomitant use of proxidant therapies with taurolidine. In my case I only use vitamin C IV but I would have to be sure if it is really doing a proxidant effect.
Daniel suggests some drugs such as sulfasalazine, retinoic acid and auranofin. I will have to look at them calmly, they all seem to have an important liver behavior ...
What do you think of my treatment line? I accept and would appreciate any suggestions.

Kind regards

@manuone

Good luck with the new addition to the treament, Manual! 

I just wanted to mention this study again, about quercetin in GBM: https://www.sciencedirect.com/science/article/pii/S0278691513007473?via%3Dihub

Anyway, the fact that your mother's condition is improving is just wonderful! 

Best,

Johan

I ment Manuel, of course!! ? 

@johan

Hi Johan,

Thanks and also for the info. We will always find studies against any molecule. I was always cautious with quercetin but I read that it can favor proliferation at low doses. In liposomal formulation I use reached 1500mg of active substance. On the other hand I combine it with sodium butyrate which show great synergy
https://www.ncbi.nlm.nih.gov/m/pubmed/31011879/

@manuone

When was your mom's last MRI?

@johan

It was in July, it was a TAC that remained the same as the previous eight months ago.
Currently having no images I rely on the clinic. Possibly after taurolidine I will try to ask for an RMI. It will be difficult for them to access, you may have to pay a private one.

@manuone

My father-in-law used to pay aprox us$500 for a MRI, but now pays just us$50 at a public clinic. So it's worth checking various places to find out what they charge.

Dear friends,

I update the treatment thanks to Daniel's latest publication on oxidative therapies! It is greatly appreciated that it improved the taurolidine therapy that I plan to implement.
The therapy will be with various intravenous treatments, not very well even how to combine, this is an idea:
2 days of vitamin c iv (50g) >>>> 2 days of 2dg metronomic 1g >>>>>> 2 days taurolidine (2 x 250 ml / day) >>>>> salinomycin iv

Drugs and supplements:

- Sulfasalazine: 1g / d (3 days prior to taurolidine)
- Canagliflozin: 100 mg (away from 2dg)
- Metformin: 1700 mg
- Sodium phenylbutyrate: 3-5g every day
- Artemisinin: 1000 mg + 1500 mg sodium butyrate
- Green tea: 2000 mg every day
- HCA: 2000 mg every day
- Lycopene 100 mg
- Doxycycline: 200 mg with vitamin c iv
- Statin: atorvastatin? simvastatin or pitavastatin?

I would like to receive your opinions with some questions:
- Is the order of intravenous treatments correct?
- Is atorvastatin better than pitavastatin? Would it be better to use piperlogumin to avoid statins? (the liver could already be very loaded)
- Hydroxychloroquine showed good synergy with salinomycin iv .... why do you not recommend it in oxidative therapy? Salinomycin also acted in ferroptosis ...?
- Would it be good to add liposomal curcumin and liposomal quercetin?

I must be cautious with the liver and not overload with drugs because some studies speak of taurolidine hepatotoxicity, sulfasalazine and statins

I will appreciate all your ideas and advice

kind regards

Hi Manuel, this looks great. I believe adding Curcumin could be beneficial, but as you know I have my doubts about using Quercetin in GBM. 

Good luck!

@johan

Thanks for your opinion Johan
In any case, quercetin absorption is very poor ..... There are very conflicting studies on this topic, remember that we will always find conflicting studies with any molecule. I really think I will discard quercetin for the poor supply

Posted by: @manuone

Dear friends,

I update the treatment thanks to Daniel's latest publication on oxidative therapies! It is greatly appreciated that it improved the taurolidine therapy that I plan to implement.
The therapy will be with various intravenous treatments, not very well even how to combine, this is an idea:
2 days of vitamin c iv (50g) >>>> 2 days of 2dg metronomic 1g >>>>>> 2 days taurolidine (2 x 250 ml / day) >>>>> salinomycin iv

Drugs and supplements:

- Sulfasalazine: 1g / d (3 days prior to taurolidine)
- Canagliflozin: 100 mg (away from 2dg)
- Metformin: 1700 mg
- Sodium phenylbutyrate: 3-5g every day
- Artemisinin: 1000 mg + 1500 mg sodium butyrate
- Green tea: 2000 mg every day
- HCA: 2000 mg every day
- Lycopene 100 mg
- Doxycycline: 200 mg with vitamin c iv
- Statin: atorvastatin? simvastatin or pitavastatin?

I would like to receive your opinions with some questions:
- Is the order of intravenous treatments correct?
- Is atorvastatin better than pitavastatin? Would it be better to use piperlogumin to avoid statins? (the liver could already be very loaded)
- Hydroxychloroquine showed good synergy with salinomycin iv .... why do you not recommend it in oxidative therapy? Salinomycin also acted in ferroptosis ...?
- Would it be good to add liposomal curcumin and liposomal quercetin?

I must be cautious with the liver and not overload with drugs because some studies speak of taurolidine hepatotoxicity, sulfasalazine and statins

I will appreciate all your ideas and advice

kind regards

Hi Manuel,

It looks very good indeed. I have the following remarks:

- Doxycycline may have anti-ROS action https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321135/

- Stains: as you know Simvastatins reaches better the brain but it has short half/time, Pitavastatin has other better properties discussed elsewhere, but I think Atorvastatin has more anti-cancer mechanisms, fair half/time and fair BBB penetration. So probably Atorvastatin could be more suitable. Pieprlogumine - I am not sure about BBB penetration - maybe you can check that.

- Here is why autophagy inhibitors do not fit well with Ferropoptosis https://www.nature.com/articles/cr201695 This is why I would not combine Hydroxychloroquine with a strategy that is expected to deliver results via ferropoptosis too. But it's a matter of feeling. My point was that this strategy focused on ROS could touch ferropoptosis as well and I would allow that to happen by just not using hydroxychloroquine. But since beyond theory no body knows what is best 100%, one other way is to do half of the regime without Hydroxy and the other half with Hydroxy.

- Salinomycin would also fit perfectly here indeed.

Btw, I very much respect the view of Johan and also on Quercetin - this is why I wanted to say that we should stay with the recommendation not to use Quercetin. But than I remember a case of a cancer patient with glyoblastoma - I met her in person - she received a few months of combo Curcumin and Quercetin liposomal intravenous every day 5 days/week. She never disclosed the entire regime and location where she received this as she was more secretive working with Pentagon - nevertheless the results were great, tumour was almost gone after some months of treatment - I should try to contact her to see if I can get anything more - I think she was getting also DMSO. Anyway, I would at least use Curcumin liposomal. I think that is a good idea indeed.

I hope this answers the questions.

Kind regards,
Daniel

Posted by: @daniel

But than I remember a case of a cancer patient with glyoblastoma - I met her in person - she received a few months of combo Curcumin and Quercetin liposomal intravenous every day 5 days/week. She never disclosed the entire regime and location where she received this as she was more secretive working with Pentagon - nevertheless the results were great, tumour was almost gone after some months of treatment - I should try to contact her to see if I can get anything more - I think she was getting also DMSO. Anyway, I would at least use Curcumin liposomal. I think that is a good idea indeed.

I hope this answers the questions.

 

Kind regards,
Daniel

That's very interesting, would be great to find more about her treatment.

Btw, Quercetin is a OATP inhibitor, and I believe it can influence Atorvastatin uptake.

Thanks friends for your opinions,

I see clearly adding liposomal curcumin (every day) and DCA to make pressure in 2 DG days.
I think the IV order could be better using vitamin C before taurolidine, perhaps seen like this:

2 DG metronomic_____vitamin c iv_____taurolidine_____salinomycin

Do you know of any negative interaction of sulfasalazine with these iv treatments?
Lycopene in a dose of 100 mg a day is not a powerful antioxidant?

Thanks Daniel and johan

- Doxycycline may have anti-ROS action https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321135/ <<<<<<<< I should not use doxycycline so if I am purely looking for an oxidative treatment ? . It is the same doubt that I have with lycopen high dose.....

Yes Johan, I will try to contact the lady and see if I get a response.

Kind regards,
Daniel

Posted by: @manuone

- Doxycycline may have anti-ROS action https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321135/ <<<<<<<< I should not use doxycycline so if I am purely looking for an oxidative treatment ? . It is the same doubt that I have with lycopen high dose.....

This is difficult to decide Manuel as Doxy has other benefits. But maybe I would take a brake now from it. Metformin and Salinomycin are already part of the cocktail as as mito inhibitors.

@daniel

Lycopene? Is other important anti oxidant in this case you include it in pro-oxidant therapy...why?

@manuone That is a fair question Manuel. With that, I wanted to fully address Mevalonate Pathway .... although it is not part of the category of strong anti-oxidants, you could consider taking it out of the cocktail.

In general, when it comes to avoiding anti-oxidants in combo with pro-oxidant treatments I would apply strict rules and avoid the following:

1. known strong anti-oxidants (which mainly include those I mentioned in my recent post such as NAC, ALA, GSH)
2. potential relevant anti-oxidants with very good bio-availability (a new one we may have in this category is Doxy - I need to investigate this more)

Thanks Daniel,

I understand, I will focus on purely oxidative therapy. I think that I can eliminate lycopene and doxycycline since I think that the cocktail will improve in theory enormously taurolidine.

Thank you for all..your opinions have great value for me.

Best whises

https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-9-372#MOESM2
I am going to rule out sulfasalazine in our particular situation, the 50% increase in cerebral edema in the patients in this study is a very important fact to consider

@manuone

Thanks a lot for the reference Manuel. I just included a note related to the post on pro-oxidant strategy https://www.cancertreatmentsresearch.com/modulating-the-yin-and-yang-energy-of-cells-to-fight-cancer-pro-oxidant-strategy/

This is such a good example showing that my posts are meant to develop or consolidate concepts but each person should check these concepts and see how they fit to their special situation.

Kind regards,
Daniel

This is all that at the moment I consider to complete the intravenous treatments of salinomycin / vitamin c / taurolidine / metronomic 2 DG:

- metformin 1700 mg
- Canagliflozin 200 mg
- atorvastatin 40 mg
- sodium phenylbutyrate 4 g
- celebrex 400 mg
- tamoxifen 80 mg (only in some cycles)
- hydroxychloroquine (only in some cycles)
- green tea 2000 mg
- milk thistle 1000 mg
- dha 2500 mg
- HCA 2000 mg
- artemisinin 1000 mg + sodium butyrate 1500 mg (only in some cycles)
- liposomal curcumin + 2000 mg oral curcumin

* I consider not using GLUT inhibitors in vitamin C iv sessions such as metformin, canagliflozin and milk thistle
* I am clear not to use canagliflozin near metronomic 2 DG
* You should not abuse atorvastatin, artemisinin, and tamoxifen to avoid overloading the liver.

Is it correct to use the rest of supplements always?
Would you add or remove something?

Thanks and a big hug

@manuone

Hi Manuel,

Regarding the use of supplements with chemo, I finally think this is a simple guide that we can use regardless of the strategy:

• strong anti-oxidants like NAC, ALA, etc. should not be taken 6-7 days before and after chemo;
• anti-oxidants known to have pro-oxidant effects (like Quercetin, Curcumin, etc.) should not be taken 2-3 days before and after chemo (even when we know they have pro-oxidant action).
• pro-oxidants or others widely known to bring good benefit to radio/chemo can be continued during chemo/radio. Examples are: Omega 3, Aremisia Annua, Silver Solution

I also added here https://www.cancertreatmentsresearch.com/modulating-the-yin-and-yang-energy-of-cells-to-fight-cancer-pro-oxidant-strategy/ a proposal on how to go when the chemo is oral and taken every day, i.e. not pulsed.

In this way we should simplify a bit the complexity of all these. 

Regarding the list you put together, I think it looks good. If I would add anything on this list would be:

- one more drug that is known to address well the second part of the fermentation pathway (just in case)

- coloidal silver 

Have a Happy Ester and a big hug to you and your mom!

Kind regards,
Daniel

@daniel

Do you think there could be exceptions to this approach based on pathology and chosen plant drugs?

For example, below article stating synergy of ldh-a inhibitor (oxamate) and doxorubicin in sarcoma cell line:

https://www.spandidos-publications.com/or/31/6/2727

"We detected that lactate dehydrogenase-A (LDHA) is highly active in chondrosarcoma cells and chondrosarcoma patient samples compared with normal chondrocyte cell lines and primary human chondrocyte. Moreover, chondrosarcoma cells exhibited elevated levels of LDHA expression under doxorubicin treatment."

"Finally, we reported a synergistic effect produced by incorporating doxorubicin with glycolysis inhibitors-oxamate in the combined treatment of chondrosarcoma cells in vitro and in vivo."

Screening of natural plants for LDHA inhibition potency (extensive ranking list) shows Camellia Sinensis among others (which is potent anti-oxidant):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3903096/

And another article reports in-vitro synergy between EGCG and dox in osteosarcoma cell lines:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389193/

"We found that EGCG targeting LncRNA SOX2OT variant 7 produced synergistic effects with Doxorubicin on osteosarcoma cell growth inhibition."

last article didn't check catechin from glucose metabolism point of view(and it might not be the case in for osteosarcoma).