Silibinin effective for brain metastases in lung cancer

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daxys
Silibinin effective for brain metastases in lung cancer

This seems to be an option for everyone with brain metastases (inform your doctor as it is quite new) ) Here are links to research done in Spain in 2017 where patients brain mets improved significantly by taking silibinin :
https://academic.oup.com/annonc/article/28/suppl_5/mdx366.035/4108588 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5077992/

The results show great improvement - threefold compared to normal situation. It was after WBRT , but it might work on its own according to theoretical part of the research. Dr. Barrera-the head of this research informed me that silibinin was effective on its own in a mice model.
Silibinin (also called silybin) is a major constituent of silymarin - milk thistle extract. In the research they used Legasil - a silibinin extract with increased bioavailability (through Eurosil 85 formulation). Bioavailability could be a problem with regular extracts.
Legasil also contains vitamin E, which according to Mr. Barrera does not probably play any role here.

Jim C Forum Mod...
Jim C Forum Moderator's picture
Hi daxys,

Hi daxys,

Although this preliminary data indicates that this is a subject which warrants further study, as the authors point out there is a need for additional research before silibinin can be endorsed as an effective therapy. Many cancer treatments which seem effective in small trials, and especially in animal models, fail to deliver on their initial promise.

In addition, silibinin can have effects on the liver, as well as the absorption rate of certain drugs, so I would caution against beginning such therapy without consulting your oncologist. With that in mind, the portion of your post which recommends a beginning dose has been removed.

JimC
Forum moderator

Jim C Forum Mod...
Jim C Forum Moderator's picture
Hi daxys,

Hi daxys,

Please do not misunderstand my comments. I appreciate and applaud your desire to bring this possible treatment to the attention of GRACE members. I agree that silibinin has passed the early hurdles in the vetting process, which are more fully described in Dr. Weiss' post on How to vet a treatment idea But as Dr. Weiss states, many proposed treatments are based on solid scientific theory, work well in animal models and show promising results in small trials, only to fail when more rigorously tested in large, randomized trials. We would hope that this in not the case with silibinin, and that it becomes a valuable weapon in our fight against cancer. But that has not yet been proven.

I am pleased that you have added your recommendation that patients discuss possible treatment with silibinin with their oncologist. As you can see from this page from the Memorial Sloan Kettering Cancer Center, there are factors which should be considered by patients and physicians before beginning the use of this (or any other) supplement.

Also, regarding funding for clinical trials of easily available, inexpensive supplements vs. expensive drugs developed and marketed by pharmaceutical companies, while it is true that Big Pharma spends huge sums of money funding trials for drugs they hope will be big sellers, trials are also funded by the government and by private foundations, as Dr. Weiss points out. And many trial concepts are created by dedicated research oncologists whose only motivation is to find effective new treatments. A search of clinicaltrials.gov reveals 24 clinical trials of milk thistle-related treatments for various conditions, despite the lack of profit motivation.

Again, thank you for bringing this promising treatment to the attention of the GRACE community.

JimC
Forum moderator

onthemark
Hi daxys,

Hi daxys,

I'd also like to thank you for your informative posts and links on milk thistle related treatment for brain mets.

It certainly does seem promising and if I ever were to get brain mets it is something that I would definitely look into.

How is it working for you Mum? Is she on osimertinib and Silibinin?

onthemark
Hi daxys,

Hi daxys,

What a big relief to hear that your mum has a meningioma rather than a brain met from lung cancer. Your situation is rather complicated. Was thinking that lesion was cancer a factor in switching off of Afatinib or was that done for some other reasons.

There are clinical trials looking at alternating 1st generation TKI's with 3 rd generation. 1 month of one and then one month of the other etc. This is thought to control larger populations of cancer cells and at the same time reduce the odds of resistance developing. There are indications from animal studies that resistance may not develop at all.

I'll respond about my thoughts about silibinin. If it also increases the time to resistance developing then perhaps there is no harm that she had it for 7 weeks, whilst you were waiting for new treatment to start. There's been a surprising amount of research on silibinin over the years. I still have to look into it some more to understand even why it is supposed, theoretically, to be effective.

Are you following your mum's CEA? My oncologist also likes to measure these values and now I go in once a year for scans and blood tests. I have some long lasting side effects from cisplatin but my scans are all stable.

When was your mum's last two ct scans and when did she stop taking afatinib? I am not so sure an xray can measure effectiveness in all cases but it might give some information if the differences are big.

Keep us posted!

onthemark
Hi daxys,

Hi daxys,

Thanks for sharing the information of silibinin and brain mets.

For people on TKI's who get a response, the key to long lasting treatment is preventing, delaying or possibly even reversing resistance. Whatever cancer cells grew since your mum stopped Afatanib in March 2018 did so without the selective pressure on Afatinib and not be under the selective pressure of resistance to it as the cells that caused small progression in the ct scan of Feb 2018.

I hope your mum gets a good result on the xray. When is her next ct scan? You can always add silibinin later if that makes sense to you and your doctor.

Here are three links on clinical trials with protocols for alternating TKI's:

https://clinicaltrials.gov/ct2/show/NCT03122717
https://www.jto.org/article/S1556-0864(17)32030-0/abstract

and also this is interesting.
https://www.frontiersin.org/articles/10.3389/fmed.2016.00076/full

There are a couple of other references regarding alternative TKI's that I have come across but am not finding them now.

onthemark
Hi daxys,

Hi daxys,

Thank you for sharing JunC's experience. Since your mum responded to Afatinib there is a good chance it is still a medication that can work for her at the right time and in the right combination.

I hope you see terrific results on the xray tomorrow. Keep us posted!

onthemark
daxys,

daxys,

I would just rely on the xray to prove there is no very bad result or exceptionally good result, like NED. Indeed remarkable turnaround in metastatic lung cancer has been seen in case reports of TKIs and personal experiences one can read about on the web, although that is not the most common situation.

I thought it was an urban myth that those who get side effects from TKIs are more likely to respond, but then I found this 2013 paper: "Skin Rash could Predict the Response to EGFR Tyrosine Kinase Inhibitor and the Prognosis for Patients with Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis"

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055128

They were not studying Tagrisso though, which has a milder side effect profile. It seems there are similar types of published results for immunotherapies as well.

Did you mum also have no side effects on Afatinib? I think the fact your mum was stable on Afatinib for a long time is also important to factor in as a positive prognostic. But that is just my thinking.

onthemark
Hi daxys,

Hi daxys,

I hope the next ct scan shows a good result. Is your mum still on dex?

onthemark
hi daxys,

hi daxys,

the research paper that I linked to in my previous post says that legalon is the same as thisilyn, but maybe it is outdated and that is no longer the case.

Jim C Forum Mod...
Jim C Forum Moderator's picture
Hi daxys,

Hi daxys,

I agree that it's good to be cautious in the use of supplements, especially when you are actively receiving anti-cancer treatment. There are so many supplements it's difficult to impossible to test for all interactions, and the industry is not particularly well-regulated. So I agree with your decision to avoid supplements with vitamin E and use a product for which you have been able to get detailed information on its specific formulation.

Good luck with silibinin, and please keep us updated.

JimC
Forum moderator

onthemark
Hi daxys,

Hi daxys,

Are you certain that Legalon Madaus Forte uses the Eurosil 85 extraction? This information should be on the patent information leaflet. I have not been able to get an answer myself to this question.