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Our Conversations Webinar Series is an opportunity to link national experts in colorectal cancer and other related fields to you, right in the comfort of your own home. The programs are designed to empower you to play a leading role in your healthcare management.

Last month, our webinar focused on 5-FU, the most common colorectal cancer treatment, where we explored the history and benefits, as well as the causes and treatment of toxicities that arise in many patients. Participants listened in and asked the following questions.

Q: How can I work with my oncologist to get weekly "cfDNA" (circulating free DNA), or "tDNA" (tumor DNA) blood sampling done, AKA "liquid biopsies", to determine if 5-FU or Xeloda (capecitabine) is working, rather than anxiously waiting for CT, MRI, and/or PET scans only twice a year? Wouldn't liquid biopsies immediately show my oncologist and I exactly what is working and when, or what is NOT working, and when? And, as a result, we could stop one thing and start something else much sooner and with much more info?

A: Unfortunately we don't know the answer yet. It depends upon what setting the person is asking from - adjuvant or metastatic. For metastatic disease, we use repeat imaging to see if therapy is working, as well as CEA (carcinoembryonic antigen) testing. Think of it as a little protein that gets shed in the blood. Not everyone will have an elevated CEA, but when elevated it often correlates with the CT. I use the CEA with the CT scan to see how therapy is working. In adjuvant therapy there is nothing to see on the CT scan, so we follow the CEA to see if the patient’s disease has recurred. CEA is not a perfect test, 20% of metastatic patients will not be elevated, so it's not the definitive way to follow someone, but it is one of the better ways to follow.
In terms of other tests, there are circling proteins called CA's and there are Circling Tumor Cells or CTC's. There was the hope that doctors would follow how patients respond to each treatment by measuring number of CTCs which would also help look at recurrence. For multiple cancer types including colorectal, it's probably not as helpful for multiple reasons. Most people have very low levels of circulating tumor cells. What has evolved is circulating free DNA which is easier to measure, but we don't really know how to use it. So can this be used to follow a recurrence, or for someone who is receiving treatment, and for metastatic disease as a way to follow that disease? It is just unknown.
Cancer cells are normal cells that turned abnormal through mutations. At the time of initial diagnosis with a biopsy, we can test for some of those mutations as some are very relevant to certain treatments used today. RAS is a gene that if mutated, a set of drugs called Cetuximab - Erbitux or Panatibumab - Vectibix, will not work. Some patients have a BRAF mutation, and we know there are some strategies to specifically treat those types of cancers. We also know that as cancer cells keep growing, some of those mutations may change over time. One option is to keep rebiopsying the patient. Another option is to use recirculating free DNA to measure if there are different mutations emerging. This is really an area of research where we hopefully will understand how this all works.  

Q: I tolerate 5FU well but have stopped oxaliplatin and more recently Avastin due to toxicity. I'm worry that my significant metastatic tumor load will increase rapidly in the absence of Avastin, but my teeth are in desperate need of some attention. How effective is 5FU alone in the presence of soft tissue tumors, lymph node tumors, and multiple, sub centimeter lung nodules? Is it foolish to take a long break from Avastin in order to prevent failure to heal from dental procedures? Are there any natural supplements that can increase the efficacy of 5FU?

A: Here is some background on how drug combinations were originally tested for those with metastatic colorectal cancer. The only choice was 5fu with Leucovorin or another moduling agent. We treated the patient as long as it was controlling the disease or if toxicity became limiting. When these relatively newer combinations with Irinotecan and Oxaliplatin came around, adding Avastin with Cetuximab became the norm. Clinical trials were similar; you stayed on the drugs as long as they were working. If they stopped working or a patient lost tolerability you would think about other options. That isn't how drugs for chemotherapy for lung cancer initially developed. Reasonable Strategy in randomized trials was patients would receive 4 to 6 cycles of treatments then stopped and doctors watched. For lung cancer, now there's maintenance therapy and other therapies used. For colorectal cancer, some strategies have evolved because of neuropathy from Oxaliplatin. While Oxaliplatin clearly has beneficial effects on tumors, it unfortunately also sees a really high number of patients who will eventually develop neuropathy which can be limit their continued use of it.
Strategies developed where Folfox is used for a while, then stopped, or just continued 5FU or even take a full treatment break. Various trials were run for continuous treatment, stopping one of the drugs, continuing maintenance therapy, and some people call it chemo lite or taking a treatment holiday. Looking at the data and which trial, each of those strategies are very reasonable but at the end of the day care is taken so survival isn't compromised. Individual situations are different. Some trials suggest doing some maintenance therapy is better than doing a full treatment break. I always emphasize when we treat metastatic disease there definitely needs to be balance in how a patient feels with improving survival while maintaining quality of life. Quality of life may be maintained very well with maintenance therapy, but it may also be important to take some time for treatment breaks. 

Q: I've heard TAS-102 described as a cousin of 5FU. Is that true? How are these drugs similar? How are they different?

A: The Trade name for TAS-102 is Lonsurf; it was first used in Asia before approval here. It is a cousin if you will of 5FU as well as Capecitabine, but just a bit different. It affects the same pathways and is metabolized like 5FU, so there is similarity in terms of pathway. The registration trial the FDA used to approve the drug occurred where patients first received all other standard chemotherapies for metastatic colorectal cancer. TAS-102/Lonsurf showed a survival benefit and it was clear some patients did but some patients didn't show benefit. Why it works in someone who has already received months or even years of 5FU is a little unclear. We need to understand if it somehow reverses some of the resistance some may develop from 5FU.

Q: Why should aspirin be avoided whilst on 5FU?

A: Talk to your physician if there are concerns regarding platelets. If someone has a cardiac condition and need aspirin, they should certainly continue their aspirin.  Always consult your physician. There are studies like ours about Celecoxib which is not aspirin, but it does affect platelets. There are also studies looking at aspirin, that it could also have an anti-treatment effect. It has to be used with some caution because when the platelets drop with the 5fu it’s not that it is necessarily contraindicative. Similarly Coumadin is something that people may need to continue. I wouldn't stop taking aspirin while taking 5fu but it's really something to discuss with your oncologist. 

Q: I am a stage 4 colon cancer patient who has been on folfiri every 2 weeks since 2014 and has been going home with pump all that time. Earlier this week I went for another treatment and my clinician team changed my pump to something called a dosi-fuser. When I asked why, I was told Medicare does not cover pump any longer and my pump was replaced with a dosi fuser. I was wondering if you have any feedback on this device? 

A: When we started doing combination therapies with Oxaliplatin and Irinotecan, particular with Irinotecan, as it was approved before Oxaliplatin in the US, we had been giving a bolus regimen of just 5FU once a week. A regimen called IFL came about - a weekly regimen of 5FU Leucovorin and Irinotecan. In Europe, Folfiri and Folfox were more commonly used, and some of that was our lack of familiarity of pumps, insurance coverage, etc. When Folfox came out it was clear it was better to give as an infusion as opposed to a bolus. It also became clear that IFL was pretty toxic and Folfiri was less toxic, and that's when practices started using pumps and insurance started covering. Some providers only cover certain pumps. Definitely a reasonable question to ask your oncologist or your oncology pharmacist, as I am not that familiar with that particular pump.

Q: Can you take Xeloda with irinotecan?

A: There have been regimens combining capecitabine with irinotecan - some consider the toxicities too overlapping and more toxic (than FOLFIRI or CAPEOX).

Q: How can I work with my oncologist to be properly tested for "DHP deficiency" (dihydropyrimidine dehydrogenase deficiency) well in advance, BEFORE taking ANY intravenous 5-FU or oral capecitabine (Xeloda), as part of FOLFOX, FOLFIRI, FOLFOXIRI, CAPOX, or CAPOXIRI chemo treatments?

A: You can discuss with your oncologist re: testing - testing can take a few weeks to return and decisions re: therapy may be needed sooner.  Further, the test is not a yes or no answer - it predicts more likely or less likely to have toxicities but not definitive. 

Q: How effective is folfiri as adjuvant therapy for rectal cancer recurrence? How many cycles are recommended? I have had four but cannot continue due to an injury to my ureter during surgery. I have had several complications from it.

A: FOLFIRI is not used in adjuvant therapy since there were 3 trials in colon cancer as adjuvant therapy with 5-FU and irinotecan, all of which were negative.

Q: How many times do you suggest a CEA test and how accurate do you think it is for predicting cancer growth?

A: Depends on the setting - I do not test during adjuvant therapy but follow guidelines after adjuvant therapy in surveillance of every 3 months x 2-3 years then every 6 months till 5 years;  for metastatic disease, there is a lot of variation in practice and you should discuss with your oncologist his/her preferred strategy.

Q: I am a 36 Stage IV colon cancer survivor dx at age 30 with tumors in the sigmoid colon and liver, with peritoneal seeding.  I underwent 9 months FOLFOX every two weeks with 48 hr pump, with weekly Erbitux.  I then had HIPEC with RFA to my liver, then 1 year of Xeloda for maintenance. I have been over 4 years cancer free and almost 3 years off of chemo. My primary question is what are the long term side effects of all of that treatment?  How can I help my primary doctor help me?  I have pain….pain in shoulder, in hands, feet back and pelvis.

A: I am happy to hear re: 4 years cancer free - that's great news.  Re: long term effects, probably the most relevant one is from oxaliplaitn and neuropathy that may or may not fully resolve as time goes by (but we know it can take months to years).  Re: your pain, not sure that should still be from your chemo and if is worth discussing with your PCP and oncologist. 

Q: I am Stage 4 with mCRC in Liver and Lungs. On Folfox for 26 treatments, just switched to folfiri last week. Is there a time frame for the maximum amount of straight treatments?

A: There really is not a maximum amount - depends on many factors, including efficacy, toxicity, goals, and balance of quality of life.

Q: Why would a patient get the pills vs. the 5FU and would the switch ever occur from 5FU to the pills specifically for stage IV with mets to liver?

A: Capecitabine and IV 5-Fu have similar efficacy in randomized trials - some patients do not tolerate capecitabine (oral pills) and there are preferences amongst different oncologists on which to start with - it is important to discuss with your oncologist rationale for recommendation of one versus other.

Don’t forget, the Colon Cancer Alliance serves as a source of information about colon health. If you have additional questions about colon cancer screening or are in need of support, please contact our free Helpline at (877) 422-2030. We’re here to help.  



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