5FU as second line?

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mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

5FU as second line?

Postby mpbser » Tue Jun 11, 2019 2:09 pm

Has anyone done, or heard of, only 5FU as a second-line treatment?

I would be very interested in learning the rationale behind such a decision. Thanks in advance!
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU

CF_69
Posts: 49
Joined: Sat Dec 22, 2018 9:44 pm

Re: 5FU as second line?

Postby CF_69 » Tue Jun 11, 2019 2:43 pm

I’m not sure if this is what you’re asking, but I’m currently taking Xeloda alone for adjuvant chemo.
47 year old male
Distal sigmoid near rectosigmoid junction adjacent to upper rectum
Adenocarcinoma
2.8 x 1.8 x 3.5 cm
G2
T3N0M0 after pathology
CEA 1.9
Xeloda / radiation x 25
Laparoscopic LAR April 2019
0 of 12 nodes
Stage 2A
5 cycles of adjuvant Xeloda
MRI on liver for 2mm hypodensity not suspicious.

zephyr
Posts: 222
Joined: Thu Aug 18, 2016 7:31 am

Re: 5FU as second line?

Postby zephyr » Tue Jun 11, 2019 5:32 pm

After Folfox, I was on 5fu and Avastin for a while. I stopped the Avastin after 2-3 months because of issues healing and was on 5fu only for several months before going on Folfiri.
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
Posts: 100
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: 5FU as second line?

Postby Rock_Robster » Tue Jun 11, 2019 7:44 pm

mpbser wrote:Has anyone done, or heard of, only 5FU as a second-line treatment?

Just to clarify, do you mean true ‘second line’ - as in after failure (progression) on first line (FOLFOX or FOLFIRI)?

Or is this more about adjuvant or maintenance chemo?

Thanks, Rob
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.
MSS, MMR-proficient, mutated in NRAS (G13R).
CEA: Oct-18 = 12; Nov-18 = 14, Mar-19 = 2.4
11/18 - 6 cycles neoadjuvant FOLFOX
12/18 - DVT, started clexane
3/19 - Liver resection, R0
4-5/19 - Long-course pelvic chemoradiation (45 Gy w/ Xeloda)
07/19 - Planned restaging scans and ULAR w temp ileo

mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

Re: 5FU as second line?

Postby mpbser » Wed Jun 12, 2019 5:05 am

I guess I was using the term "second-line" without a full understanding of what it means. It may be easier to put my question another way:

Has anyone done, or heard of doing, only 5FU (monotherapy) instead of Folifiri/etc after surgery for a liver met recurrence? My signature below may provide a clue.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU

Rock_Robster
Posts: 100
Joined: Thu Oct 25, 2018 5:27 am
Location: Melbourne, Australia

Re: 5FU as second line?

Postby Rock_Robster » Wed Jun 12, 2019 5:32 am

Thanks mbpser, I now understand.

My understanding is that when 5-FU monotherapy is used in an adjuvant setting (ie post curative surgery) it is typically for one of a few reasons, including:
- tumours with relatively low risk of recurrence (eg stage II without high-risk features)
- diminished patient performance score (eg elderly, frail or comorbidities)
- Inability to tolerate oxaliplatin (eg allergy, or dose-limiting side effects reached)

There is also some practice to use 5-FU (or Xeloda) as a ‘maintenance’ therapy to either sustain or prevent recurrence, either as a cyclical therapy at full dosage, or at a lower dose continuously (aka metronomic chemo). I don’t think the latter is especially common, esp. outside Europe, and esp. in a metastatic setting (ie stage IV).

There may be other reasons or rationales - others can no doubt add.

Given everything your husband as been through, I presume you’re looking for a ‘lighter’ chemo alternative? (Given it doesn’t seem that he failed either FOLFOX or FOLFIRI).

Cheers, Rob
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.
MSS, MMR-proficient, mutated in NRAS (G13R).
CEA: Oct-18 = 12; Nov-18 = 14, Mar-19 = 2.4
11/18 - 6 cycles neoadjuvant FOLFOX
12/18 - DVT, started clexane
3/19 - Liver resection, R0
4-5/19 - Long-course pelvic chemoradiation (45 Gy w/ Xeloda)
07/19 - Planned restaging scans and ULAR w temp ileo

User avatar
LPL
Posts: 635
Joined: Fri Apr 22, 2016 12:49 am
Location: Europe

Re: 5FU as second line?

Postby LPL » Wed Jun 12, 2019 12:13 pm

DH @ 65 DX 4/11/16 CC recto-sigmoid junction
Adenocarcenoma pt 35x15x9mm G3(biopsi) G1(surgical)
Mets 3 Liver resectable
T4aN1bM1a Stage IVa 2/9 LN
MSS, KRAS-mut G13D
CEA & CA19-9: 5/18 2.5 78 8/17 1.4 48 2/14/17 1.8 29
4 Folfox 6/15-7/30 (b4 liver surgery) 8 after
CT: 8/8 no change 3/27/17 NED->Jan-19 mets to lung
:!: Steroid induced hyperglycemia dx after 3chemo
Surgeries 2016: 3/18 Emergency colostomy
5/23 Primary+gallbl+stoma reversal+port 9/1 Liver mets
RFA 2019: Feb lung met

mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

Re: 5FU as second line?

Postby mpbser » Wed Jun 12, 2019 4:02 pm

No, I hadn't seen that. Thanks, LPL!

I am familiar with the sad statistics cited in that website: even with the addition of leucovorin, only about 20 percent of mCRC patients respond to treatment, compared to approximately 10 percent response to 5-FU alone (J Clin Oncol 1989;7:1419-1426)... oxaliplatin was found to have synergistic effects when combined with 5-FU + leucovorin therapy, called FOLFOX therapy, raising the response rate in mCRC patients to approximately 38-45 percent (Semin Oncol 1999;26(6):647-662, J Clin Oncol 2008;26:2013-2019) (Figure 1). With the exception of biologic agents that can help increase overall survival when paired with FOLFOX treatment (Oncology 2008;75(3-4):215-223), there have been no significant advances to therapies for mCRC for decades.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU

User avatar
juliej
Posts: 2986
Joined: Thu Aug 05, 2010 12:59 pm

Re: 5FU as second line?

Postby juliej » Wed Jun 12, 2019 5:17 pm

mpbser wrote:Has anyone done, or heard of doing, only 5FU (monotherapy) instead of Folifiri/etc after surgery for a liver met recurrence? My signature below may provide a clue.

The only systemic chemo I did after my liver resection was Xeloda, which is the oral form of 5FU.
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 3/18/2019, CEA<1

mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

Re: 5FU as second line?

Postby mpbser » Thu Jun 13, 2019 12:34 pm

Julie,

Do you happen to know if your CC was tp53 mutated? I read, again as I have seen this expressed a number of times in various journal articles over the past couple years, that "CRC with mutated TP53 is resistant to 5-FU" in this extremely interesting article https://www.ncbi.nlm.nih.gov/pmc/articl ... 3/#cit0021 Even more disturbing, "Overall, 5-FU may induce prosurvival autophagy that partly reverses its apoptosis-inducing effect."
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU

User avatar
juliej
Posts: 2986
Joined: Thu Aug 05, 2010 12:59 pm

Re: 5FU as second line?

Postby juliej » Thu Jun 13, 2019 6:33 pm

mpbser wrote:Julie,

Do you happen to know if your CC was tp53 mutated? I read, again as I have seen this expressed a number of times in various journal articles over the past couple years, that "CRC with mutated TP53 is resistant to 5-FU" in this extremely interesting article https://www.ncbi.nlm.nih.gov/pmc/articl ... 3/#cit0021 Even more disturbing, "Overall, 5-FU may induce prosurvival autophagy that partly reverses its apoptosis-inducing effect."

Interesting article! Here's another one along the same line of thinking. My tp53 was mutated but the type of mutation is equally important (tp53 mutations occur most commonly in exon 7, but codons 175, 213, 237, 238, 241, and 331 are also targets). F10, which is mentioned in the article, is a DNA-directed FP polymer that is significantly more potent than 5FU.

While TP53 is frequently mutated in CRC, the significance of TP53 gene mutations for response of CRC patients to 5-FU-based chemotherapy regimens remains under investigation. TP53 mutation status is not currently used to direct therapy decisions[2], however there is increasing evidence that not all TP53 mutations exert equivalent effects on tumor aggressiveness or chemotherapy response. In particular, there is evidence that TP53 mutations that confer “gain-of-function” by altering the DNA-binding domain of p53 may be particularly deleterious as they cause increased tumor aggressiveness and metastasis in animal models[37,38]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320232/
Stage IV, liver/lung mets 8/4/2010
Xelox+Avastin 8/18/10 to 10/21/11
LAR, liver resec, HAI pump 11/11
Double lung surgery + ileo reversal 2/12
Adjuvant Xeloda 3-9/12
VATS rt. lung 12/21/12 - benign granuloma!
NED 3/17/12 to 3/18/2019, CEA<1

mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

Re: 5FU as second line?

Postby mpbser » Fri Jun 14, 2019 6:29 am

Who would have thought that it could get even more complicated??? [/sarcasm]

Thanks for sharing. I look forward to spending the weekend reading about this and 5FU monotherapy. [/not sarcasm]

My husband's tp53 mutation was at exon 7. I'm not sure if that is a good or bad thing.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU

mpbser
Posts: 905
Joined: Wed Apr 19, 2017 11:52 am

Re: 5FU as second line?

Postby mpbser » Fri Jun 14, 2019 6:56 am

Looking at that article you shared, julie, and see that "Significant resistance to 5-FU resulted from p53-loss or from gain-of-function (GOF) mutation (R248W)." My husband's mutation is [at least in the "first primary colon tumor"] "TP53 c.745A>G (p.R249G), exon 7 - in 34% of 279 reads." I assume that G (p.R249G) is also a gain-of-function mutation.

Ugh. I may just call the Center for Advanced Molecular Diagnostics where his test was done.
Wife 4/17 Dx age 45
5/17 LAR
Adenocarcinoma
5 x 4 x 1 cm
low grade
T3 N2b M1a
Stage IV A
8/17 Sub-total colectomy
2nd tumor 5.5 cm T1 N0
lymph nodes: 9 of 96
CEA: 2.9 to 2.2
MSS/MSI-L
Lynch no; KRAS wild
Immunohistochemsistry Normal
Tumor: MTOR, APC, TP53
Fall 2017 FOLFOX shrank the 1 met in liver
1/18 Liver left hepatectomy seg 4
5/18 CT clear
12/18 MRI shows 1 liver met
3/7/19 Resection & HAI
4/1/19 Folfiri & FUDR
5/13/19 HAI pump catheter dislodge, nearly hemorrhaged to death
6/10/19 5FU


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