Silibinin in combination with Tarceva - 1295091

Hi masalovai, Welcome to Grace. This is a comment by JimC one of our moderators on the subject, "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." in the 2nd post of the thread, http://cancergrace.org/topic/silibinin-effective-for-brain-metastases-i…

Knowing how the vetting process works you'll have a better understanding why it's not a good idea to automatically try something without going through clinical trial process. Good ideas on paper, in the lab and in animals usually lead to less than appealing results in humans, sometimes even worse outcomes.
http://cancergrace.org/cancer-101/2009/11/21/how-to-vet-a-treatment-ide…

Talk to your oncologist about it. SRS has proven to be a pretty safe and effective treatment for brain mets and is lengthening survival rates quite a bit. Of course it would be wonderful if it turns out that silibinin. Fingers crossed.

I hope you don't have the need.
All best,
Janine

Hi masalovai,

Unfortunately I don't see a big study on the horizon that is going to answer the important questions. There are several people here at cancergrace and also on inspire who are also interested in silibinin for lung cancer brain mets and delaying TKI resistance, so if you end up using it in consultation with your doctor I would be interested in hearing your experience.

Best wishes,

OTM

Hi Masalovai.

Best wishes for continued good results from the Tarceva, and a future of no brain mets regardless of the form of your treatment.

There is no need to post the actual link to the article for a restricted (for pay) publication. If you wish, you can just cite the information of the publication in your post (Title, Journal, Date, Page) and those of us who have access or want to pay can then get a ahold of it.

Thanks!
scohn

Hi masalovai,

Great to hear you have been in contact with Prof. Bosch- Barrera. I hope when the new grace website is online we can exchange private messages through the site:)

In the meantime, if you are on inspire.com my username is the same, 'onthemark' and we can pm there and exchange email addresses privately.

Thank you for your offer to send the paper, and good luck with Tarceva!

Thanks so much for the link!

scohn

It's a small world Ellina! I just sent you a note on inspire.

My personal experience with researching silibinin or silymarin for lung cancer has been somewhat frustrating. First of all there is a lot of (mixed quality) research on silibinin in medicine in general and only a small fraction of that is on lung cancer at the moment. So there are a lot of papers but only some of them are worth reading. Certainly anything published by nature.com is credible as a source of information...

Another issue is that my background is not a particularly good fit for sorting out all the information on the subject. Here are two reference though regarding silibinin lung cancer;

Cufí, S., Bonavia, R., Vazquez-Martin, A., Corominas-Faja, B., Oliveras-Ferraros, C.,
Cuyàs, E., Martin-Castillo, B., Barrajón-Catalán, E., Visa, J., Segura-Carretero, A.,
Bosch-Barrera, J., Joven, J., Micol, V., Menendez, J.A., 2013a. Silibinin meglumine, a
water-soluble form of milk thistle silymarin, is an orally active anti-cancer agent that
impedes the epithelial-to-mesenchymal transition (EMT) in EGFR-mutant non-smallcell
lung carcinoma cells. Food Chem. Toxicol. 60, 360–368. https://doi.org/10.
1016/j.fct.2013.07.063.

Nan, J., Du, Y., Chen, X., Bai, Q., Wang, Y., Zhang, X., Zhu, N., Zhang, J., Hou, J., Wang,
Q., Yang, J., 2014. TPCA-1 is a direct dual inhibitor of STAT3 and NF-κb and regresses
mutant EGFR-associated human non-small cell lung cancers. Mol. Canc.

Finally I believe that the Eurosil 85 patented extraction method is the only one that has solid backing in studies of humans. And I would check directly with the author of the study if any other brand were used other than the one mentioned in the paper

For those who are interested and who are able to digest any important papers it might be helpful to summarize what is . in some of them...

Personally if I thought i was out of other options I would try it... I am not sure it would be allowed in a clinical trial.

ps.. Do you know what the data was for the EGFR positives vs EGFR wild type?

Here is a related, publicly available paper that cites your nature.com:

Silibinin is a direct inhibitor of STAT3
S Verdura, E Cuyàs, L Llorach-Parés… - Food and Chemical …, 2018 - Elsevier

http://valientelab.com/publicaciones/2_food_chem_toxicol_2018.pdf

I asked Dr. Weiss, Graces vice president about this treatment. He responded, "I'm afraid that I don't have primary knowledge on this subject (which is itself a reflection on level of promise as I spend a lot of time to know about the things with most promise). One of the pharmacists (Chris Walko?) might be able to provide a more detailed answer."

I'll see if Dr. Walko has anything to add from a clinical profession's standpoint.

Hello Masalovai,

Interestingly, one of my former PhD students actually did his dissertation work on milk thistle and drug interactions.

The first consideration is that different commercial milk thistle products have different compositions of at least 7 different flavonoliganans. Silibinin products only contain silybinin A and B, but in different amounts as well. Several components of milk thistle have been shown to inhibit a common liver enzyme called CYP3A4. Erlotinib (Tarceva) is broken down by CYP3A4 so inhibiting this enzyme can result in higher concentrations of the drug in the body. While this would not decrease efficacy, it can definitely increase the risk of toxicities. This may be why higher responses were seen in the brain of patients with EGFR-mutated NSCLC tumors as higher systemic concentrations can mean higher levels in the brain (I was also a part of a study at UNC where we looked at higher doses of erlotinib and took samples of CSF to see how much was able to get into the brain).

My biggest concern is that because the different milk thistle products have different amounts of substances (and are not consistently regulated to ensure what they state on the bottle is actually in the product being sold), you can have variable inhibition of erlotinib breakdown and increased toxicity. Additionally, while the milk thistle data in the lab and in animals is supportive of liver protection, this has been conflicting in human studies. A well done trial in hepatitis C patient who took 3-5 times the normal recommended dosages of milk thistle did not show improvement in liver function (JAMA 2012;308;274-282).

I certainly support the enthusiasm behind these investigations and hope that larger trials with clarify these benefits.

I would not recommend starting this until discussing with your oncologist who can also look at other medications you are taking to assess the risk of drug interactions.

Best wishes,
Dr. Walko

Thanks to everyone for this informative thread!