What does "5-FU clearance" mean? Re: Xeloda

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zephyr
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What does "5-FU clearance" mean? Re: Xeloda

Postby zephyr » Sun Apr 14, 2019 1:37 pm

I should be able to figure this out but I'm stumped. I found a Medscape article about Xeloda that states:
During the first cycle of capecitabine development, three concomitant drugs were found to affect 5-FU clearance. Paracetamol and morphine increased 5-FU clearance by 26% and 41%, respectively, and loperamide decreased 5-FU clearance by 31%


Paracetamol is the European version of Tylenol. It works better on me than Tylenol so I brought home several boxes a few months ago. That said, the two are claimed to be identical so the "clearance" issue might apply to Tylenol too. Loperamide, as many of us know all too well, is Imodium. Before I take either one, would someone please translate the quoted sentence for me?

Thanks.
Nov-2009 Early stage CRC found during routine colonoscopy
2010, 2011, 2014 Follow up colonoscopies, all clear
Jun-2016 CRC found during routine follow up colonoscopy, surgery, Stage 4, KRAS, MSS, inoperable lung mets
Aug-2016-May-2018 Folfox, 5FU & Avastin, 5FU, Folfiri & Cyramza
Aug/Sep-2018 YAG laser surgeries (Germany) on both lungs, 11 nodules (9 mets) removed
Nov-2018 clean CT scan
Mar-2019 New lung nodules
April-2019 Xeloda + Avastin

mpbser
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Re: What does "5-FU clearance" mean? Re: Xeloda

Postby mpbser » Sun Apr 14, 2019 2:03 pm

I believe that the term essentially means "to be gotten rid of" i.e. " to clear" the body. For chemo to be "gotten rid of" within the body, it is via metabolism and excretion (out through the kidneys -- pee!). Here is an article I looked at to see if I am on the right track: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375329/
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5/17 - Lap left hemi
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
lymph nodes: 9 of 54
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry: Normal MLH1, MSH2, MSH6, and PMS2
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zephyr
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Re: What does "5-FU clearance" mean? Re: Xeloda

Postby zephyr » Sun Apr 14, 2019 2:29 pm

mpbser wrote:I believe that the term essentially means "to be gotten rid of" i.e. " to clear" the body. For chemo to be "gotten rid of" within the body, it is via metabolism and excretion (out through the kidneys -- pee!). Here is an article I looked at to see if I am on the right track: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2375329/


Thanks, you are correct. I just found another explanation here:
https://www.nottingham.ac.uk/nmp/sonet/rlos/bioproc/clearance1/index.html

Interesting that paracetamol (and maybe Tylenol) increased clearance but loperamide decreased clearance. Presumably an increased clearance would result in less toxicity but how does that play out for efficacy? Back to research...
Nov-2009 Early stage CRC found during routine colonoscopy
2010, 2011, 2014 Follow up colonoscopies, all clear
Jun-2016 CRC found during routine follow up colonoscopy, surgery, Stage 4, KRAS, MSS, inoperable lung mets
Aug-2016-May-2018 Folfox, 5FU & Avastin, 5FU, Folfiri & Cyramza
Aug/Sep-2018 YAG laser surgeries (Germany) on both lungs, 11 nodules (9 mets) removed
Nov-2018 clean CT scan
Mar-2019 New lung nodules
April-2019 Xeloda + Avastin

Rock_Robster
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Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: What does "5-FU clearance" mean? Re: Xeloda

Postby Rock_Robster » Sun Apr 14, 2019 7:33 pm

Hi mpbser, I found the ‘Pharmacokinetics’ section of the below article very helpful for my understanding of how Xeloda works in the body, particularly the Capecitabine —> DFCR —> DFUR —> 5FU cascade. Also the relationship (or lack of) between plasma concentration levels and tumour concentration levels:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484526/
Male 37 years; Melbourne, Australia
10/2018 Dx: 3.5 cm rectal adenocarcinoma, 10 cm from verge. Well/mod diff (G1-2), T3bN1bM1a.
3 enlarged local lymph nodes and 4 liver lesions.
Mutation in NRAS (G13R; exon 2, codon 13). MSS; MMR proficient.
11/18 - 6 rounds neoadjuvant FOLFOX
12/18 - DVT, started clexane
3/19 - Liver resection, clear margins
4/19 - Planned long-course chemoradiation (25 x 1.8 Gy with 3000 mg/day Xeloda)

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GrouseMan
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Re: What does "5-FU clearance" mean? Re: Xeloda

Postby GrouseMan » Mon Apr 15, 2019 8:09 am

Increased clearance could result in less effectiveness of the 5-FU and Decreased clearance could contribute to increased side effects. One should not mess around with these variables in drug phamacokinetics. Both these drugs effect 5-FU clearance by either increasing or decreasing metabolism by liver enzymes responsible for breaking down compounds in the body for elimination. How 5-FU is dosed was optimized to minimize side effects and maximize effectiveness. So Anything that effects this is not a good thing.

Regards,

GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017


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