bad bad folfox first round. folfiri next?

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waw4
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Location: Durham, NC

Re: bad bad folfox first round. folfiri next?

Postby waw4 » Fri Sep 24, 2010 8:24 pm

I believe it's called a DPD - 'Dihydropyrimidine Dehydrogenase' enzyme deficiency.

From http://www.myriadpro.com/ (a lab test company):

DPYD - A gene that makes the enzyme primarily responsible for metabolizing or breaking down 5-FU and clearing it from the body quickly. If DPYD enzyme activity is compromised, 5-FU is cleared more slowly, resulting in a longer period of exposure and a subsequent increase in toxicity. Patients with DPYD mutations have up to a 7-fold increased risk for dose-limiting toxicity from 5-FU treatment.

According to the same site, there's also:
TYMS - An essential enzyme for DNA synthesis. If a genetic variation causes underproduction of TYMS, only a portion of the 5-FU dose binds to and inhibits this enzyme; the rest remains unbound in the body, resulting in increased toxicity. Patients with variations in the TYMS gene have up to a 1.4- to 2.5-fold increased risk for dose-limiting toxicity from 5-FU.

Finally, according to the same site (who's business is to do these lab tests) says:
"Up to 25% of individuals have variations in the DPYD and/or TYMS genes that are associated with an increased risk of toxicity to 5-FU."

Terry wrote:Is your sister doing Xeloda or 5FU? There is something with 5FU in certain people that they are unable to metabolize the 5FU and it is VERY toxic and has taken the lives of a few people. There is a test for it but I can't remember what it is. Maybe someone else on here will remember more details.
Bill's Colonoscopy 6/29/10; Dx Stage I or II
Surgery 7/15/10; Dx Stage III,15/32 lymph nodes
FOLFOX4 start 9/14/10; end 1/20/11 (9 tx)
Grateful for 2nd Chance NED time!

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florencedollar
Posts: 288
Joined: Sun Sep 12, 2010 12:14 pm

Re: bad bad folfox first round. folfiri next?

Postby florencedollar » Fri Sep 24, 2010 8:30 pm

Yes! They ARE testing for that.. it makes sense now. Sis told me they are testing for a genetic reason for her having such a severe reaction to the chemo.
Thank you for the info.

waw4 wrote:I believe it's called a DPD - 'Dihydropyrimidine Dehydrogenase' enzyme deficiency.

From http://www.myriadpro.com/ (a lab test company):

DPYD - A gene that makes the enzyme primarily responsible for metabolizing or breaking down 5-FU and clearing it from the body quickly. If DPYD enzyme activity is compromised, 5-FU is cleared more slowly, resulting in a longer period of exposure and a subsequent increase in toxicity. Patients with DPYD mutations have up to a 7-fold increased risk for dose-limiting toxicity from 5-FU treatment.

According to the same site, there's also:
TYMS - An essential enzyme for DNA synthesis. If a genetic variation causes underproduction of TYMS, only a portion of the 5-FU dose binds to and inhibits this enzyme; the rest remains unbound in the body, resulting in increased toxicity. Patients with variations in the TYMS gene have up to a 1.4- to 2.5-fold increased risk for dose-limiting toxicity from 5-FU.

Finally, according to the same site (who's business is to do these lab tests) says:
"Up to 25% of individuals have variations in the DPYD and/or TYMS genes that are associated with an increased risk of toxicity to 5-FU."

Terry wrote:Is your sister doing Xeloda or 5FU? There is something with 5FU in certain people that they are unable to metabolize the 5FU and it is VERY toxic and has taken the lives of a few people. There is a test for it but I can't remember what it is. Maybe someone else on here will remember more details.
Sis to 'lil sis (pict in avatar)
DX'd stage IV CC w/liver mets -age 45- 8/26/2010
Port Folfox started-9/8/2010
Colonic stent-9/30/2010
10/13-Team agrees-postpone chemo after 2 rounds
10/26 colon/liver resection
12/14/2010-Folfiri/Avastin
NED NED NED!!!!!

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florencedollar
Posts: 288
Joined: Sun Sep 12, 2010 12:14 pm

Re: bad bad folfox first round. folfiri next?

Postby florencedollar » Fri Sep 24, 2010 8:41 pm

So if she does have the genetic reason for being unable to tolerate Folfox FU, then what are her options? Xeloda?
Sis to 'lil sis (pict in avatar)
DX'd stage IV CC w/liver mets -age 45- 8/26/2010
Port Folfox started-9/8/2010
Colonic stent-9/30/2010
10/13-Team agrees-postpone chemo after 2 rounds
10/26 colon/liver resection
12/14/2010-Folfiri/Avastin
NED NED NED!!!!!

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Bev G
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Location: Quechee, VT

Re: bad bad folfox first round. folfiri next?

Postby Bev G » Sat Sep 25, 2010 12:00 am

Florence: My understanding is that Xeloda is converted to 5FU in the body, but maybe it somehow bypasses that enzymatic step (not sure how it could do that though, but it's been decades since I took biochem) If she has an issue with that enzyme, I'm not sure she would be able to take any form of 5FU. I was so,so sick from chemo they tested me for that and I was OK, so hopefully she will be too--enzymatically I mean. Well, and in every way too, of course!

All the best, Bev
58 yo Type1 DM 48 years
12/09 Stage IV 2/22 nodes + liver met, colon resec
3 tx FOLFIRI, liver resec 4/10
9/10 6 mos off chemo, Neg PET&CTC CEA nl
2/11 finished total 10 rounds chemo

9/13 ^17th clean PET/CT NED for now


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