@manuone for notification
https://www.cancertreatmentsresearch.com/community/postid/6599/
Hi Manuel - I am jumping in here with my first post on the forum. I am trying to help my wife fight GBM, and would love if you can share some of the wisdom you have gained in treating this disease with me. Also, sorry about the passing of your Mom. My wife was hospitalized due to a urinary tract infection that went systemic early on in this 10 month battle, and we also have incontinence/mobility issues. My wife’s tumor is inoperable due to being spread out in the thalamic region. Fortunately, we have some moderate shrinkage from standard care and possibly due to the plethora of supplements and medications I ask her to take daily. My concern is that she will not be able to qualify for many clinical trials because of her weak condition and tumor location. Our oncologist does not want to do much prior to the tumor progressing. This is the sad state of Western medicine where they treat the symptoms instead of the cause. I hate to sit around and wait.
JW
@jdubw Hi JW, sorry to hear about your wife's situation. My father-in-law had a glioblastoma 20 years ago and I've written about it here: https://synergiesforcancertreatments.blogspot.com/p/17-year-glioblastoma-survivor.html
thanks for sharing your website. The CAM info is really good. I plan on looking into increasing our melatonin usage if we could get some additional benefit.
Your Dad’s recovery is remarkable and makes those meds more interesting. We will probably end up doing CCNU as the next chemo if we go that route. The temozolomide was ridiculously hard on her, and I doubt we will want to do it again. Tamoxifen is slightly interesting, the studies were not stellar, maybe it is more effective in tumors with certain genetic markers and in concert with the other meds. My wife is high on the EGFR marker (common in breast cancer).
I don’t know what to think about the sodium phenbutyrate. Seems like it should be in more clinical trials. I saw a trial where there was one complete response, and not much happening to the other participants. Maybe this is a genetic marker thing. It sure does seem attractive if we could figure it out. Maybe it works best in concert with chemo. Have you heard other successes with it?
@jdubw my father in law also had a tough time on temozolomide, if I remember well he did 3 rounds had to stop because of progression. We thought CCNU would be equally tough or worse as that was what we´d been told but instead, he was able to cope with the entire 6-month cycle very well. His oncologist even wanted to add a few more rounds which I felt would do more harm than good and he stopped and just continued with melatonin and tamoxifen.
Regarding Phenylbutyrate, insurance company AETNA states the following "Since sodium phenylbutyrate has been approved by the FDA for treatment of other indications, physicians can prescribe it for patients without any danger of legal sanctions or need for compassionate use exemptions. However, there is no adequate evidence in the peer-reviewed published medical literature demonstrating that the use of sodium phenylbutyrate improves the clinical outcomes of patients with other indications such as cancers of the prostate, breast, or cancers other
than acute promyelocytic leukemia and malignant glioma. "
https://pubmed.ncbi.nlm.nih.gov/12241121/ " The patient was treated with radiation therapy and Procarbazine-CCNU-Vincristine (PCV). However, the tumor progressed and extended to the corpus callosum with midline shift, refractory to four cycles of continuous 72-h infusion of BCNU/Cisplatinum. Additional enhancing lesions appeared in the left frontal and left temporal lobes. The patient was started on sodium phenylbutyrate, 18 g daily in three divided oral doses, and reduced to 9 g/day and eventually to 4.5 g/day to eliminate mild, reversible side effects. Four years later, the patient has a KPS functional score of 100%. Phenylbutyrate is a well-tolerated, oral agent that shows potential for the treatment of malignant gliomas."
Here on the forum, Manuel (@manuone) gave PB to his mother, she exceeded her prognosis by many years. And adifer the father of a child with brainstem glioma https://www.cancertreatmentsresearch.com/community/postid/4204/ "The overall volume shrinkage of the tumor was somewhere around 50% after phenylbutyrate was added to the mix (2-axis improvement as Daniel said). With visible functional improvement. We stopped phenylbutyrate though when he developed hydrocephalus. "
"oral tamoxifen is an appealing target for the heavily pre-treated patient population of recurrent high-grade glioma and further studies should be explored." https://scholars.direct/Articles/neuro-oncology/ino-3-007.php?jid=neuro-oncology
"This pilot phase II study would suggest that the concomitant administration of the pineal hormone MLT may induce objective tumour regressions in metastatic breast cancer patients refractory to TMX alone." https://pubmed.ncbi.nlm.nih.gov/7710954/
In addition, melatonin reduces the toxicity of tamoxifen. "Melatonin also reverted the liver, ovarian and uterus toxicity induced by tamoxifen. The results have demonstrated that tamoxifen when used as combination therapy with melatonin serve as an effective anti-breast cancer molecule with minimum liver, ovarian and uterus toxicities." https://pubmed.ncbi.nlm.nih.gov/7710954/
You can see why combination therapy is so important when you start adding the different benefits of specific combinations.
Note that my fil didn't use PB he took A10 which is no longer available. But PB is metabolized into phenylacetylglutamine and phenylacetate, and these molecules are the L-Glutamine Derivative (A10) as per the product description, which is a mixture of phenylacetylglutamine and phenylacetylisoglutamine in a ratio of 4 to 1. At the dose we gave him this would be equivalent to approx 5 grams of PB, in 3 doses. Note that the products also have other ingredients including ornithine which, in my view, is of importance since the combination of PB and ornithine works synergistically to detoxify ammonia. https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.22897
So he was also getting 500mg of ornithine in addition to the A10, and approx 100mg of vitamin B2 (study suggests that higher dietary intake of thiamine, riboflavin, nicotinic acid, and folate are associated with a decreased risk of glioma).
In this study in mice, a combination of magnolol and honokiol was more effective than Temozolomide.
(magnolol https://liftmode.com/magnolol-powder/)
thanks for the helpful info!
I am wondering if you could test blood ammonia level to predict phenylbuytrate efficacy?
We tried Magnolia early on, but it acutely exacerbated a psychological problem. I think the tumor was causing increased physiological problems for at least 6 or 8 months before diagnosis. We have psychiatric meds to help control the situation, and so I have been reluctant to add magnolia back in.
you could test blood ammonia before and after a course of PB (and ornithine) however that's just a snapshot of ammonia in the blood, which doesn't really give an idea of ammonia production in tissues but useful information nonetheless.
Have you tried pure magnolol (isolated from magnolia off.)?
@jdubw But I don't know if there's any level that can give an indication of the efficacy of the substance unless ammonia is extremely low which may indicate it would be less useful as a glutamine/ammonia scavenger.
Although I doubt you'd find low ammonia if you'd tested for it now.
I believe we used the magnolia extract that was 90% honkiol + magnolol. The side effect may have just been transient for many reasons. She is much more psychologically stable now, so I am hoping to have a better experience with it.
Magnolia looks good on paper, but there are not clinical trials to back it up. The amount of benefit is speculative. Valproic Acid is another one that looks good on paper. Some of the studies indicate a modest survival benefit. The question then becomes is it worth adding into the mix.
The struggle with CAM is that there is at least a hundred supplements that have some scientific indication to possibly benefit a Glioblastoma patient. I have not come across anyone that has been sure of a major benefit such as shrinkage from one or more supplements. This could be because Glioblastoma patients are so heavily medically treated that it is hard to discern.
What would you say are the top 5 supplements that one could take to improve the odds of beating Glioblastoma? (assuming that medical oncology treatments are still being employed)
That's a very good question. If Temodal fails, your oncologist might propose CCNU/BCNU, PCV, or Avastin/irinotecan.
Whatever the combination your oncologist proposes, we're talking about overall survival for recurrence in terms of months, not even years.
Wouldn't you agree that they too only offer modest survival benefits?
Yet, there's a huge difference. You can be absolutely sure that's what they offer. They have randomized clinical trials to support the dismal survival benefit. Meaning, that's it.
I read a study yesterday about an artificial intelligence program that is capable of predicting survival time in cancer patients with 80% accuracy just based on the oncologist´s notes and medical information of the patient. It's that predictable.
I am sorry to be so blunt, but once you realize this, you either accept what they offer or challenge it. You're trying to improve the odds, but you're trying to do it the way they do. You're looking for clinical trials and studies, confirmation of efficacy in human trials. You won't find much.
Please watch this video, and look at the IV bag @ 1:03:11. It says A10. That's antineoplastons or as an alternative, phenylbutyrate, as a prodrug for A10.
https://youtu.be/AZELzO5jfC8?t=3664
Tori was cured of brainstem glioma, which according to Wikipedia has a 0% 5 years survival rate. Yet you won't find her case in a clinical study or review.
My father-in-law's oncologist has only one long-term survivor, and he's been an oncologist for over 30 years. He's the only one, and he took antineoplastons and melatonin, the others didn't.
Here's my top 5.
1. Phenylbutyrate + Ornithine + Vitamin B2
2. Tamoxifen
3. Melatonin
3. Magnolol + Honokiol. (not magnolia extract)
4. Citric acid
5. Boswellia
Thanks for sharing your insights. I have learned that the big hitters are generally needed to really make a dent in the tumor. I discounted antineoplastons after my initial research, but I am moving that back into the big hitter category (vaccines, immunotherapies, chemo, radiation, berburicin, etc..). I tend to consider CAM herbs/dietary supplements as small hitters, but they can potentially be big hitters and can potentiate the big hitters (chemo/radio-sensitizers). I’ve also been thinking that if you combine enough small hitters that you can potentially produce a big hitter. I tend to thing that generally you want as many hitters, small and big, as you can to maximally affect the tumor without creating unexpected problems.
We have been doing Boswellia from early on, and plan to keep doing it. We usually do 1 gram twice per day. I have trouble with increasing the dose very high because it requires a lot of pills. My wife does not like to take pills very much, and I already give her so many. We are currently doing Vitamin C infusions 3 x week @ 75 grams.
I haven’t seen anything noteworthy on Vitamin B2, but I just found how B3 looks like it is worth adding into the mix. I am wondering what form of niacin to use… or maybe just all the forms
check this out
Your diagram is really cool and I will need to spend some more time thinking about it. Although I did want to know your thoughts on Acetazolamide? We were taking that to potentiate the Temozolomide, but did not see a clear benefit without the chemo.
@jdubw Niacin is a very interesting molecule, for one it's small and especially useful in brain cancer I think. It's near the top of my list of supplements on that gbm blog page, I've even referenced the research you mention.
Abram Hoffer, MD, one of the founders of orthomolecular medicine, was a big proponent of the use of niacin/niacinamide in various diseases, including cancer. On Audible you can listen to his book "Niacin, the real story" It's available for free. Hoffer preferred niacin but often used niacinamide mainly because patients didn't like the flush of niacin, which can be very uncomfortable.
Combining enough small hitters is what my blog is about, not just randomly but by taking advantage of synergies.
If you're using vitamin C you might also want to explore combinations that could make it more effective, for example, magnesium:
https://synergiesforcancertreatments.blogspot.com/p/vitamin-c.html
We have been doing Boswellia from early on, and plan to keep doing it. We usually do 1 gram twice per day. I have trouble with increasing the dose very high because it requires a lot of pills. My wife does not like to take pills very much, and I already give her so many. We are currently doing Vitamin C infusions 3 x week @ 75 grams.
I haven’t seen anything noteworthy on Vitamin B2, but I just found how B3 looks like it is worth adding into the mix. I am wondering what form of niacin to use… or maybe just all the forms
check this out
Your diagram is really cool and I will need to spend some more time thinking about it. Although I did want to know your thoughts on Acetazolamide? We were taking that to potentiate the Temozolomide, but did not see a clear benefit without the chemo.
I'd recommend mcsformula's Boswellia, it has 200mg Boswellic Extract standardized at 30% AKBA in a liposomal formulation. I believe it has the highest AKBA you'll find and you might even want to get in contact with them as Daniel told me he was making an even stronger formulation that would be available only via physicians, I believe this stronger formula will be tested in a study with glioblastoma patients.
I'd use Acetazolamide in combination with mTOR inhibitors such as rapamycin.
Vitamin B2 is part of the antineoplaston A10 formulation we used so I'd use it in combination with phenylbutyrate and ornithine.
@jdubw Niacin is a very interesting molecule, for one it's small and especially useful in brain cancer I think. It's near the top of my list of supplements on that gbm blog page, I've even referenced the research you mention.
Abram Hoffer, MD, one of the founders of orthomolecular medicine, was a big proponent of the use of niacin/niacinamide in various diseases, including cancer. On Audible you can listen to his book "Niacin, the real story" It's available for free. Hoffer preferred niacin but often used niacinamide mainly because patients didn't like the flush of niacin, which can be very uncomfortable.
Combining enough small hitters is what my blog is about, not just randomly but by taking advantage of synergies.
If you're using vitamin C you might also want to explore combinations that could make it more effective, for example, magnesium:
https://synergiesforcancertreatments.blogspot.com/p/vitamin-c.html
citric acid reduces ammonia, as does phenylbutyrate, ornithine, and naringin (on the diagram as IL6 inhibitor). Ammonia can induce IL6 via TLR4
Natural dietary compound naringin inhibits glioblastoma cancer neoangiogenesis
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310324/
"we have shown that naringin exerted significant antitumor effects on s.c.gliomas at a dose of 120 mg/kg/day"
human equivalent dose approx 535mg for 55kg human
Cancer cell intrinsic TIM-3 induces glioblastoma progression
https://www.cell.com/iscience/pdf/S2589-0042(22)01601-7.pdf
I've edited the diagram to reflect this. As you can see Narining is also useful here.
@j thanks again for all the helpful info. I am checking on adding or pre-loading magnesium with the Vitamin C.
Also, per info I got from the Burzynski clinic, they are claiming that about 54% of GBM patients experience 25% or greater shrinkage from sodium phenylbutyrate combined with other medications (could be chemo etc..). They claim much higher with Antineoplastons. Still that number is impressive considering the side effect profile of phenylbutyrate is vastly better compared to chemo alone.
The problem I am seeing with Naringen is it gets metabolized by the liver and degraded by the intestine. So, who can say how much Naringen is getting across the BBB. The benefit of the subcutaneous tumor mouse test is that it does not need to cross the BBB. Now maybe the Naringen metabolites would cross the BBB and do some goood. It is hard to say. Also, I am not familiar with the science behind the conversion method used. It seems like a low dose for a human. If you went off a straight linear model it would be like 6 grams of Naringen.
It's been 20 years but I remember that when I researched I estimated a 15 to 30% chance of getting a good response from A10. As you mention, low toxicity is an important factor.
Naringin crosses the brain blood barrier.
Dose conversion between species is complicated but there are established calculations to give an indication of such a dose e.g. https://dosecal.cftri.res.in/index.php
in my view, this is useful as an indication of what dose to use to start with but I think it's usually at the low end, In addition, the route of administration varies and sometimes it's simply not possible to extrapolate any useful dose from animal studies.
That's one fo the reasons I find synergies so appealing as there's usually an important dose reduction to try and replicate an anticancer effect found in animal studies, or even in vitro.
in relation to BBB, it might make sense to use DHA and naringin together, both work on IL6 and it might enhance uptake into the brain.
Suppression of Proliferation of Human Glioblastoma Cells by Combined Phosphodiesterase and Multidrug Resistance-Associated Protein 1 Inhibition
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471536/
"Disrupting cyclic nucleotide-signaling through phosphodiesterase (PDE) inhibition may be a promising way of suppressing glioblastoma growth."
"our results suggest that theobromine, taken orally, crosses the blood brain barrier in sufficient quantities to exert its effects as a phosphodiesterase inhibitor in the brain."
Theobromine, the primary methylxanthine found in Theobroma cacao, prevents malignant glioblastoma proliferation by negatively regulating phosphodiesterase-4, extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B
https://pubmed.ncbi.nlm.nih.gov/24547961
very cheap supplement and only low doses are needed (can be toxic at higher doses) bulksupplements dot com sells it as powder.
@j glad you mentioned Theobromine. I have sprinkled it in once in a while, but I was waiting until I developed a new combination plan to really use it consistently. My interest in Theobromine was because I wanted to find a suitable alternative to the much studied drug, Rolipram. Unfortunately, Rolipram, is just a research drug used for testing out theories, and should not be digested; however there is a company making a unique conjugate involving Rolipram and Perilla Alcohol. Unfortunately, it is not yet available for even a clinical trial.
I may start a new thread and ask for your input when I reassemble the plan for all the supplements to try to get increased benefit.
actually back to the topic of this thread: I am looking at using Hydrogen gas inhalation at night. I figured that I can get away with something like 800 ML if it is being used for 8 - 10 hours straight. I would hate to spend so much money and take the risk of a 3L purchase to China going bad, if I can get similar results with less cost and from a reputable company. Any thoughts on lower dose over longer time approach?
@jdubw I have very little knowledge about hydrogen gas, from what I've read the 800-900ml hydrogen therapy machines look equally good for the anticancer purpose, a few months ago I emailed the authors of a Chinese study, I emailed them a few times but no response. In particular, I was interested in how the patient in one study I read was doing now, I think it was lung cancer. Also, one of the concerns I have is why they chose 3L. And then it happens that you can only get that machine for a small fortune in China.
Metabolic-targeted Combination Therapy With Dichloroacetate and Metformin Suppresses Glioblastoma Cell Line Growth In Vitro and In Vivo
https://iv.iiarjournals.org/content/35/1/341
- DCA and MET synergistically suppresses the growth of glioblastoma cells in vivo
- treatment groups with 150 mg/kg/day DCA, 75 mg/kg/day MET, or both.
- Tumor volume was evaluated every other day for 22 days. On day 18, no significant reduction in tumor growth was observed; however, on day 22, all treatments showed a significant reduction in tumor volume compared with the control group, suggesting that each drug alone and their combination can reduce tumor growth (Figure 4A). However, only the c ombination therapy achieved a statistically significant clinical result with that treatment group having longer overall survival compared with the control or monotherapy groups (overall survival benefit (mOS=29.71 days vs. 20 days control mice)
- DCA alleviated the increase in lactate production induced by MET. (again clearly demonstrating metformin increases lactate production, that's clearly an issue with metformin)
We hypothesized that when the drugs are applied as a combination therapy, lower concentration of each drug is needed in order to obtain a similar cytotoxic effect compared to monotherapy. Micromolar concentrations of drugs are highly desirable in clinical practice, especially in oncology. However, only at high doses, DCA and MET synergistically suppressed cancer cell proliferation. These results supplement other authors’ findings, where only high concentrations could inhibit cancer (34, 35, 48).
I have not really looked into DCA yet, so I’m not clear on the potential mechanism. I did read something about it possibly affecting the liver in combination with Arteminsin. I’ve tried Arteminsin occasionally, but not very much, as my concern is getting across the BBB in enough quantity while not beating up the liver too much.
I think I asked our Dr. about Metformin on the first visit. He did not like it, so I went with Berberine.
Speaking of Lactic Acid, I was looking mop that up, knowing that it is fuel for the tumor. In doing so, I saw some interesting research on Carnosine wrt GBM. I can’t remember if that was effective via Lactic Acid. Weightlifters take Beta-alanine so that it will convert into Carnosine in the body. The Carnosine mops up lactic acid to improve workouts.
@jdubw I didn't know that, weightlifters and bodybuilders are really some of the smartest people when it comes to health.
I've attached a diagram with synergistic combinations, it's for TNBC but it might give you some ideas. Also, I think TNBC and GBM have a lot of similarities. Of course, there is the issue with the BBB, but then again there's also the gut-brain axis.
I agree with your concerns and care for the health of the liver, with a compromised liver it becomes tough to keep ammonia down.
Combination Treatment with the GSK-3 Inhibitor 9-ING-41 and CCNU Cures Orthotopic Chemoresistant Glioblastoma in Patient-Derived Xenograft Models
This gel stops brain tumors in mice. Could it offer hope for humans? This is not an option available right now but good to be aware of:
Hydrogel delivers intracranial immunotherapy together with chemotherapy.
https://hub.jhu.edu/2023/04/24/mouse-brain-tumors-glioblastoma/
@j nice chart, thanks!
I've updated the chart. mTOR inhibition is probably best done in parallel with AKT/PI3K inhibition.
