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Adjuvant chemo regimen? Strategies?

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Adjuvant chemo regimen? Strategies?

Postby jdepp » Mon Mar 30, 2009 9:26 am

I know a lot of us are on adjuvant chemo. I'm curious about your regimens & how you came to choose them, especially if they involve biologicals where long-term PFS and OS data is obviously not yet available.

I had 6 rounds of neo-adjuvant Folfox with Erbitux and am now doing 8 rounds of exactly the same combination. (I know I'm an advanced case, but 14 rounds of oxi in all seems daunting. Among other things, I'm hoping my liver & my nervous system can take it.)

My onc seemed perfectly willing to consider switching my biological from Erbitux to Avastin. Erbitux attacks the EGFR pathway and Avastin goes after the VEGF, and switching would give my cancer a new look. We decided against doing that, however, mainly because it seemed like I was still responding to Erbitux before surgery. Sir Onc wants to maximize the benefit from that regimen & I guess I do, too (though on some level it feels, ahem, like a rash decision).

So here's a question I have not seen much discussed in the research: what considerations come into play in the strategy for choosing chemo to fight microscopic disease in the absence of visible solid tumors? Most studies don't seem to make any major oncological distinction between the situations -- "solid tumor plus microscopic disease" vs. "microscopic disease only" -- and perhaps none is to be made. Still, when you're going after an enemy that flies under the PET and CT radar, it seems like a different situation that might call for different approach.
Colon dx 8/08 @ 41
Poorly diff. 12+ liver mets, 19/28 LN
Colon rsx 8/08
14 Folfox-Erbitux, 10/08-8/09
PVE 1/09
Liver rsx 2/09
lung & LN mets 10/10
Folfiri-Avastin 10/10 - 4/11
Xeloda-Avastin 4/11 - 4/13
Xelox-Erb. 5-7/13. UFUR 10/13 ->
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Re: Adjuvant chemo regimen? Strategies?

Postby meeko » Mon Mar 30, 2009 10:55 am

I am stage 2A and my adjuvant chemo is just 5fu/leucovoran. It may be considered the lightweight chemo but its been hard for me. If there is a side effect...I get it. I wonder why I am doing it because there is no visible signs of cancer...I have done 6 so far. But fear of the rogue cells has kept me going.
I dont know anything about the tough stuff but wanted to give info from this end. I admire all of you who take the rough stuff... not sure I could.
rectal cancer 9/08
LAR 10/1/08
2nd surgery for peritonitis and abcess 10/08/08 w/ temp ileo
stage 2A (t3) N0/16 M0
total of 8 rounds of 5fu/Leucovoran-- 5/09
Reversal and Hysterectomy 10/09/09
Married, 2 daughters
So far ..so Good!
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Re: Adjuvant chemo regimen? Strategies?

Postby justsing » Mon Mar 30, 2009 11:46 am

For adjuvant chemo, you are better of with the Oxi if you can take it and it's still working. There is some research indicating that Irinotecan doesn't work as well in the adjuvant setting. So that's one decision that's pretty easy.

My onc is of the opinion that you don't change a regimen if it's working. So that would argue for the Erbitux.

For me it wasn't a tough decision tree. My cancer was resistant to Oxi and I'm KRASmt. So FOLFIRI and Avastin it is!
justsing, 46
Stage IV
colon resection 12/07
Liver resection 04/08
Phase I vaccine trial
liver, lung LN mets
tried Oxi, Iri and Avastin
now trying new chemo combos then sir spheres
College prof in theatre & voice
2 girls 18 & 14, one son 10
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Re: Adjuvant chemo regimen? Strategies?

Postby myrta » Mon Mar 30, 2009 11:54 am

I am not a doctor, but I have heard that chemo is effective against quickly dividing cells, not against
dormant or quiescent cells....what if quiescent colon cancer stem cells are left?
Lots of unanswered questions...
however, if your chemo seemed effective before surgery, it is reasonable to take it after chemo...
myrta
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Re: Adjuvant chemo regimen? Strategies?

Postby Ivona » Mon Mar 30, 2009 12:39 pm

I stand corrected, but I thought that the biological treatments (Erbitux, Avastin) are only used for patients with existing tumours???

In my case, since none of my scans (two CT's and one MRI) showed any tumours after surgery, I was given the 'standard' adjuvant therapy of FOLFOX. After 4 rounds and increasing side effects (constant nausea and hand/face neuropathy) my onc switched me to XELODA, which so far (knock on wood! 8) ) I've been tolerating much better.
dx'd Oct '08 (age 48)
T3bN2Mx
9/23 LN's
resection Nov '08
Folfox Jan '09 - March '09
Xeloda March 24/09 - July 6/09

"Yesterday is history, tomorrow is a mystery, but today is a gift. That is why it's called 'the present'. "
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Re: Adjuvant chemo regimen? Strategies?

Postby myrta » Mon Mar 30, 2009 3:47 pm

oops--I meant
"it is reasonable to take it after surgery"


Also, immunotherapy could be an option for those who had resection of a tumor, but it is poorly researched---
myrta

Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF
Journal Cancer Immunology, Immunotherapy
Publisher Springer Berlin / Heidelberg

Issue Volume 57, Number 7 / July, 2008
Category Original Article
DOI 10.1007/s00262-007-0431-z


PDF (519.3 KB)HTMLFree Preview

Original Article
Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF
Nobuto Yamamoto1, 5 , Hirofumi Suyama2, Hiroaki Nakazato3, Nobuyuki Yamamoto1 and Yoshihiko Koga4

(1) Division of Cancer Immunology and Molecular Immunology, Socrates Institute for Therapeutic Immunology, Philadelphia, PA 19126, USA
(2) Nagasaki Immunotherapy Research Group, Yokoh, Nagasaki, Japan
(3) Yokoyama Gastroenterology Hospital, Nagoya, Japan
(4) Nakagawa Hospital, Fukuoka City 811-1345, Japan
(5) Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, 1040, 66th Ave, Philadelphia, PA 19126-3305, USA

Received: 26 October 2007 Accepted: 21 November 2007 Published online: 6 December 2007

Abstract Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32–50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.
Keywords Colorectal cancer - Macrophages - Macrophage-activating factor - Immunotherapy - Deglycosylation - α-N-acetylgalactosaminidase - Immunosuppression
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Re: Adjuvant chemo regimen? Strategies?

Postby Gaelen » Tue Mar 31, 2009 5:50 am

myrta wrote:I am not a doctor, but I have heard that chemo is effective against quickly dividing cells, not against dormant or quiescent cells....what if quiescent colon cancer stem cells are left?


Myrta, chemo is to some extent effective against the more slowly dividing dormant/quiescent cells. It's important to remember that even within that category, some cells are more dormant (or more actively dividing) than others.

This article might help explain the multi-activity level of various types of cells:
http://www3.interscience.wiley.com/jour ... 1&SRETRY=0

jdepp wrote:I know a lot of us are on adjuvant chemo. I'm curious about your regimens & how you came to choose them, especially if they involve biologicals where long-term PFS and OS data is obviously not yet available.


Actually, none of my adjuvant (post-surgery) chemos have involved biologics. My oncologists are holding them in reserve, bigger guns to save in case I present active tumors again. The last biologic I had was part of my neo-adjuvant (pre-surgery) chemo, FOLFOX+Avastin, my very first chemo regimen. The last adjuvant chemo, the one I just ended, was plain-vanilla 5FU+Leucovorin. The adjuvant chemos in between were all some variation (in succeedingly lowered doses) of Folfiri. Dr. Personality prefers Folfiri, which is why after surgery I was switched to that regimen (I'd also reached max tolerated dose or MTD of oxaliplatin after 16 cycles.)

My onc seemed perfectly willing to consider switching my biological from Erbitux to Avastin. Erbitux attacks the EGFR pathway and Avastin goes after the VEGF, and switching would give my cancer a new look. We decided against doing that, however, mainly because it seemed like I was still responding to Erbitux before surgery. Sir Onc wants to maximize the benefit from that regimen & I guess I do, too (though on some level it feels, ahem, like a rash decision).


Well, 'rash' decision or not :roll: :) it's usually considered a good plan by my oncologists (both of them) to get all of the mileage out of a given drug that I can tolerate. So, for instance, since I tolerated folfiri really well for a looong time, I got it for 13 months (26 systemic treatments) before the liver resection, and then 3 months (6 systemic treatments) after the liver resection. And then Dr. P optimistically tried it after my surgery last April, and after one month (only two systemic treatments), my local onc removed the irinotecan and took me down to 5FU+Leucovorin for the balance of treamtnets (5 more months, 10 more treatments.) Dr. P agreed; I've finally developed immunohistamine sensitivity to irinotecan, so that's now off the table for me.
Be in harmony with your expectations. - Life Out Loud
4/04: dx'd @48 StageIV RectalCA w/9 liver mets. 8 chemos, 4 surgeries, last remission 34 mos.
2/11 recurrence R lung, spinal bone mets - chemo, RFA lung mets
4/12 stopped treatment
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