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Lonsurf and repurposed drugs  

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Daniel
(@daniel)
Admin
Joined: 5 years ago
Posts: 917
10/07/2020 3:02 pm  

I did a research for somebody yesterday on this drug used often as a 3rd line in colon and colorectal cancer - I found some relevant info on combo of repurposed drugs and Lonsurf that may help others, so here I share then:

Lonsurf (Trifluridine/Tipiracil)

Trifluridine is incorporated into DNA during DNA synthesis and inhibits tumor cell growth.
Tipiracil prevents the degradation of trifluridine via thymidine phosphorylase (TP) when taken orally and also has antiangiogenic properties

Notes:

Using Metformin and/or Cimetidine may be or not suitable with Lonsurf - better avoid until clear

Tipiracil is a substrate and inhibitor for the organic cation transporter 2 (OCT2) and the Multi-antimicrobial extrusion protein 1 (MATE1) and these transporters therefore may be involved in the elimination of tipiracil in urine. The concomitant use of a substrate and/or an inhibitor of OCT2 and MATE1 may influence tipiracil and trifluridine exposure (trifluridine exposure is correlated with tipiracil exposure) and patients may be deprived from optimal therapy. Since OCT2/MATE1 substrates (e.g. metformin) and inhibitors (e.g. cimetidine) are often and inevitably prescribed in mCRC patients (e.g. metformin in +/- 13% of all patients) the effects on Lonsurf exposure or the possible inhibitory effect of Lonsurf on OCT2/MATE1 substrates ‘in vivo’ must be investigated to study its clinical relevance. https://www.trialregister.nl/trial/8067

Doxycicline may help the effectiveness of Lonsurf

Thymidine kinase 1 (TK1) is thought to be important for the incorporation of Trifluridine into DNA, resulting in DNA dysfunction and cytotoxicity. TK1 expression was efficiently induced by treatment with doxycycline for 1 day, and the expression level correlated well with the concentration of doxycycline. Furthermore, the effect of doxycycline on TK1 expression persisted for 4 days. https://www.nature.com/articles/s41598-019-44399-6

Dipyridamole mar reduce the activity of Lonsurf

Trifluridine incorporation into nuclear DNA in human cancer cell lines was effectively blocked by the nucleoside transporter inhibitor dipyridamole (DPM), which inhibits both hENT1 and hENT2 activity https://www.nature.com/articles/srep25286

Omeprazole prior to Lonsurf may help increase its effectiveness

Trifluridine is a very weak base https://pdf.hres.ca/dpd_pm/00000133.PDF
Weak bases are inhibited by acidity around tumors and reducing that can increase the tumor penetration by Trifluridine as discussed here https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/
And please see these idea incorporate in a successful clinical study https://www.cancertreatmentsresearch.com/medicine-to-lower-stomach-acid-added-to-chemo-improves-breast-tumor-response-rate/

 


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Lizardgirl
(@lizardgirl)
Joined: 2 months ago
Posts: 2
11/09/2020 4:40 pm  

Hi Daniel,

I was wondering if you would be able to offer any guidance with my mom’s case.

She has stage IV colon cancer with mets to peritoneum and liver, she is currently on lonsurf and has stable disease, but we are concerned that once she stops responding to that she will be out of options.

She is in very good physical and mental health given her diagnosis, and is open to trying anything that could help.

Thanks in advance for your time!


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Daniel
(@daniel)
Admin
Joined: 5 years ago
Posts: 917
13/09/2020 10:58 pm  

Dear @lizardgirl

Thank you for your question. Please go through some of the content on this website, here is a summary https://www.cancertreatmentsresearch.com/summary-of-this-website/

After that we can have a call or you can address the questions by e-mail and I will do my best to help (at no cost, as always) and answer your questions.

Kind regards,
Daniel

 


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Lizardgirl
(@lizardgirl)
Joined: 2 months ago
Posts: 2
14/09/2020 12:04 pm  

@daniel

Dear Daniel,

It would be wonderful if I could email you. Where can I find your email address?

I really appreciate you taking the time to give me some guidance.

I’m sure I will be buying supplements from you at some point, I hope that will help you in some small way.

Thanks so much,

Kelley


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