Silibinin in combination with Tarceva

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masalovai
Silibinin in combination with Tarceva

Dear Moderators and Doctors

I’ve read number of exiting articles published by Spanish group about Silibinin, which is extract of milk thistle. Those papers proved that Silibinin can prolong time to Tarceva resistance and their recent publications proved that Silibinin reduces Brain Mets in lung cancer if used concurrently with systematic treatment.

I am currently on Tarceva for two months and really worry about possibility of brain mets. I would like to try Silibinin, but worry that it could interfere with Tarceva in negative way.

May I please ask you to advise !

Many thanks !

catdander
Hi masalovai, Welcome to

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-in...

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-idea/

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

onthemark
Hi masalovai,

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

masalovai
Thanks OTM for your reply. I

Thanks OTM for your reply. I was communicating with main author of those publications, Prof. Bosch- Barrera and he confirmed an excellent results.

He sent me their last paper on the effect of Silibinin on Brain Mets. Unfortunately I can get a link to this article because the fees are applied to get it.

I can email it to you if you will give the email address .

scohn
Hi Masalovai.

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

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6x Carbo/Alimta; effect. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial. 10/18 start Abraxane.

onthemark
Hi masalovai,

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!

masalovai
Dear All

Dear All

I couldn’t send you the link because I received the paper in pdf format as attached file. I will try to copy the abstract later today for you to read. It’s great study ! They had a big portion of patients with egfr mutations and they did much better but one of the referees of the paper was against comparison between egfr and wild type results. So authors removed the data for egfr positives.

Onthemark , you are my friend on inspire , so you can send me your email address. My name in inspire: Ellina

Thank you for good wishes ! Wish you all the best with your treatment as well ! ❤️

masalovai
http://www.nature.com

http://www.nature.com/articles/s41591-018-0044-4

Here is the link to the abstract.

scohn
Thanks so much for the link!

Thanks so much for the link!

scohn

Wife, non-smoker, dx 4/24/15 adeno NSCLC stage IV. HER2 Exon 20. 6x Carbo/Alimta; effect. 9/15 Alimta maint; ineffect. 11/15 - Opdivo; ineffect. 4/16 - ptK7 trial; effective 1.5 yr. 9/17 Gemzar; effective 16 mo. 8/18 -TAK788 Trial. 10/18 start Abraxane.

onthemark
It’s a small world Ellina! I

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.

onthemark
ps.. Do you know what the

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

masalovai
In my correspondence with

In my correspondence with prof. Bosch , he mentioned that they used Legasil with vitamin E for all their studies. 2 capsule a day 1+1 and increase every 3 days by 1 until 1+2+1 a day.

In their last study for brain mets they had many of egfr positive patients and they show a lot better results than egfr wild type patients.

At the last stage before it was published the referee suggested that it doesn’t make big sense to compare those two groups because egfr positive show better results without silibinin as well.

This is how Prof. Bosch explained this in his correspondence. He says in this study there were more patients with egfr positive and they showed excellent results .

I will speak to my oncologist regarding this matter, not sure what she can say though ……..

I don’t think 5here could be negative interference from Silibinin to Tarceva efficiency, except it can help to regenerate our poor liver function.

I would be very interested to know from doctors how many of their patients use milk thistle to support their liver during treatment………

catdander
I asked Dr. Weiss, Graces

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.

dr walko
Hello Masalovai,

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

Christine M. Walko, PharmD, BCOP, FCCP
Personalized Medicine Specialist
Moffitt Cancer Center, Tampa, FL

masalovai
Dear Dr. Walko

Dear Dr. Walko

Many many thanks for your detailed reply to my question. Everything is very clear and make sense for me.

We all very much appreciate your time and effort.

Thank you ❤️

Irina

masalovai
I also would like to say

I also would like to say thank you to Moderators for their continuous support ! ❤️

onthemark
Thanks to everyone for this

Thanks to everyone for this informative thread!