Lonsurf and repurpo...
 
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Lonsurf and repurposed drugs  


Daniel
(@daniel)
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Joined: 5 years ago
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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: 5 months ago
Posts: 2
 

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: 964
Topic starter  

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: 5 months ago
Posts: 2
 

@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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ZdenekSipek
(@zdeneksipek)
Joined: 2 years ago
Posts: 18
 

Hi Daniel!

Could you please take a look at my friend´s case of metastatic colon cancer?
Could we improve the protocol with something?

Here is her summary:

"I was doing great on this cocktail and fulfiri chemo bi-weekly - shrinking everything since Feb and no growth - largest tumor was less than 1.2mm. Then I had to stop everything for an emergency ileostomy. I'm recovered and doing well - so i'm back on pill protocol and oncologist is having me try a non-infusion chemo called lonsurf (super mild compared to what i've done). Waiting for next month's PET to see if I can stay on lonsurf and its working or if I go back to infusion. I did catch a CTScan at hospital post surgery - that made me think my tumors went from mm to cm (like 1.6cm was the largest). I have 2 in liver and 2 in lungs all were under 1.2mm. My CEA has rose in the last month since I've been on lonsurf - so I'm pressing my oncologist for a PET sooner - but he wants me to stay the course for another month so they know for sure if this works or not. I'm not in any pain anywhere - and feeling good."

Supplement Dose Drug/Supplement/Per Day 

Supplement 500 mg Boswellia Extract X X
Supplement 1000 mg (x2) Hydroxy-Citrate X X
Supplement 200 mg Ursolic Acid X X
Supplement 500 mg Berberine X X X
Supplement 1000 mg Quercetin X X
Supplement 1000 mg Resveratrol X X
Vitamin x2 Capsule Vitamin D3 X X
Supplement x1 Capsule Multivitamin X
Supplement x1 Capsule Omega-03 Fish Oil X
Supplement x1 Capsule Raw Probiotic X
Vitamin x1 Capsule Vitamin B Complex X
Supplement 100 mg DHEA X X
Supplement 500 mg Green Tea Extract X X
Supplement 900 mg Alpha Lipoic X X
Drug x1 100 mg Dipyridamole X X
Drug 1/2 200mg Hydroxychloroquine X X
Drug 200 mg Mebendazole X X
Drug 500 mg Metformin X X
Over Counter 81 mg Aspirin (Baby) X
Supplement 125 mg Genistein X
Supplement 1000 mg Milk Thistle X
Supplement 1500 mg Glucosamine X X
Drug 40 mg (x2) Atorvastatin X
Supplement 40 mg Melatonin X
Supplement 1000 mg Black Seed Oil X
Supplement 2250 mg Curcumin X
Drug 100 mg Doxycycline X
Drug 4.5 ml LDN X
Over Counter 10 mg Loratadine (Claritin) X


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Daniel
(@daniel)
Admin
Joined: 5 years ago
Posts: 964
Topic starter  

Hi @zdeneksipek,

Thank you for your question.

1. I would consider removing the following:

- Dypiridamole for the reason mentioned above

- Alpha Lipoic Acid as it is a string anti-oxidant

2. I would increase the dose of 

- EGCG

- Curcumin

3. I would introduce Omeprazole due to the reason mentioned above

4. Lonsurf is usually given Days 1 through 5 and Days 8 through 12 of each 28-day. I would stop all the supplements and drugs that are expected to slow down tumor activity, during the Lonsurf brake, at least Metformin and Berberine, but probably all in order to allow Lonsurf to have higher impact when started again. After that I would immediately start to reintroduce drugs and supplements.

During the break I would maintain Doxy and Omeprazole.

5. I would consider the introduction of Ivermectin due to its impact on WNT signaling / β-CATENIN that are relevant in colon c.

6. I would consider Irbesartan https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843189/

I hope this helps.

Kind regards,
Daniel

 


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ZdenekSipek
(@zdeneksipek)
Joined: 2 years ago
Posts: 18
 

Thank you very much Daniel! 

But how about aerobic glycolysis gap after removing Alpha Lipoic Acid? 
What would you recommend?

And btw what do you think about ALA + HCA combination in the context of metastatic melanoma (in lungs)? 


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Daniel
(@daniel)
Admin
Joined: 5 years ago
Posts: 964
Topic starter  

@zdeneksipek

Hi Zdenek,

You are very welcome. Phenylbutyrate may be a better idea in this case 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551558/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102924/

I like a lot ALA and I would use it but would keep it away (several days away = about 5-7) from core therapies that may induce ROS in cancer cells.

For Melanoma, there are a few interesting case reports here https://www.cancertreatmentsresearch.com/10-cases-of-complete-remission-from-stage-4-cancers-after-using-supplements-or-repurposed-drugs/

I would also use ALA with HCA but also strongly consider immuno therapy which I usually do not like but in melanoma it can have very good results. Even when done at very low dose there is still chance for response.

Kind regards,

Daniel


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ZdenekSipek
(@zdeneksipek)
Joined: 2 years ago
Posts: 18
 

Thank you very much again Daniel! You are very kind.


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