The NIH estimates that roughly 275,000 cancer patients in the U.S. receive 5-FU, or chemotherapy drug 5-fluorouracil, annually. Up to 3% of those patients experience a toxic reaction.
If your oncologist recommends 5-FU as a cancer treatment, you’ll likely have a lot of questions. “Does this treatment make the most sense for my cancer?” “What will the side effects be like?” “How do I know it will work?”
Being diagnosed with cancer is scary. Uncertainty about treatment can make it that much more overwhelming.
But genetics can help us know and understand more. Your genes provide information on how your body might process the medications used to treat your type of cancer. Knowing your genetic makeup helps you know your body better. This helps you make informed decisions when discussing treatment options with your doctor, including 5-FU.
How Does 5-FU Work?
In the body, 5-FU stops fast-growing cells (like cancer tumor cells) from creating DNA. It is often used to treat cancers of the stomach, colon, rectum, breast, and pancreas.
5-FU is given as an intravenous injection. This means that the medication is infused into the bloodstream over several hours, using a needle or tube. Another medication commonly used to treat cancer patients, called “capecitabine” is taken by mouth and turns into 5-FU in the body.
Unfortunately, because 5-FU kills fast-growing cells, unwanted side effects can happen while taking 5-FU or capecitabine. These side effects may include diarrhea, sores in the mouth and throat, decreased blood cells, heart damage, and nerve damage. In severe cases, side effects can lead to hospitalization or even death.
The good news is that we can predict who is at higher risk for these side effects. If you know
that you are at higher risk for side effects, your doctor can adjust your dose of 5-FU. Changing your dose can help reduce the risk of frequent or severe side effects.
What Leads to Higher Risk?
Several factors can contribute to higher risk of side effects for patients receiving 5-FU. DPD deficiency is a common one.
DPD—an abbreviation for a protein called “dihydropyridine dehydrogenase”—breaks down 5-FU to remove it from the body. If it’s not working properly, there could be higher levels of 5-FU in the body, and that increases the risk of severe or even fatal side effects.
DPD deficiency means that someone has little DPD in their body, or no DPD at all. This can
happen if they have a “variant” (different version) of the DPYD gene. The DPYD gene tells the
body to make DPD, so that it can breakdown 5-FU and other similar medications.
Through pharmacogenomic or PGx testing, you can gain an understanding of your DPYD gene, and through that, how your body may respond to 5-FU.
What is Pharmacogenomic (PGx) Testing?
PGx testing tells us how your body might respond to certain medications based on your genetics. Think of “pharma” as pharmacy and “genomics” as genes. The test includes multiple genes, which helps estimate how much (or how little) protein is in your body to process certain medications.
Genes are different for every individual, so with PGx information, your doctors can more precisely choose your medication therapy. This means not just the right medication, but also the right dose of medication that you will respond to best.
In addition to testing for the DPYD gene variants, PGx testing provides results on other genes that can influence how medications are processed in your body.
This means that in addition to helping prevent side effects from 5-FU or capecitabine, these results can help guide treatment for other medications as well. This can be useful for changes to chemotherapy or changes to your usual everyday medications. It can provide valuable information that may be used into the future when your medication regimen may be changing.
Is PGx Testing for 5-FU Worthwhile?
Evidence supports it.
Although there are different ways to test for DPD deficiency, genetic testing is the most promising way to detect the deficiency. That’s because there are “variants” (different versions) of the DPYD gene that can affect how your body processes 5-FU. Some variants can increase the risk of severe side effects from 5-FU when taken at normal doses.
Several studies show that PGx testing for 5-FU is beneficial. For example, a Canadian study reduced the dose of 5-FU for a group of patients with DPD deficiency. When given 50% of the usual dose, these patients experienced the same frequency of side effects as another group of patients without the deficiency, who took the full dose. These results mean that patients with DPD deficiency should take a lower dose of 5-FU to help avoid severe side effects.
In pharmacogenomics, several groups develop recommendations for genetic testing for specific
medications. Two of the most used guidelines are the Dutch Pharmacogenetics Working Group (DPWG) and the Clinical Pharmacogenetics Implementation Consortium (CPIC). Both organizations recommend PGx testing for patients starting 5-FU.
Can I Get PGx Testing?
Talk to your doctor. Many health insurance policies cover pharmacogenomic testing, and some—including cancerŌme® from healthŌme®—let you directly request PGx testing through an online portal.
The testing process is easy and non-invasive, often with a cheek swab sample you can do at home and send in. And the information gathered helps in the short and long term. PGx testing only needs to be done once, since your genetics generally do not change. The results will be available for you anytime you need them, to make medication decisions now and in the future.
What happens after PGx testing?
Testing is the start. Interpretation helps you and your doctor use that information to optimize treatment.
At GalenusRx, our Precision Clinical Pharmacists specialize in interpreting PGx test results. We break down PGx data and what they mean, then provide recommendations to help your medications work best with the lowest risk of side effects.
For patients, this process is about as simple as the PGx test. Once our Precision Clinical Pharmacists receive your results, you can schedule a virtual visit, either by telephone or video chat, to go over your findings and recommendations. A summary of your PGx test results and medication recommendations are sent to you and your doctor.
Questions About PGx Testing or Medication Safety Assessments?
Learn more at GalenusRx.com, or contact GalenusRx.
REFERENCES
- National Institutes of Health, Public Health Service, HHS. Public teleconference regarding licensing and collaborative research opportunities for: Methods and compositions relating to detecting dihydropyrimidine dehydrogenase (DPD). Federal Register. 2008;73:FR-38233
- Diasio, RB, Offer, SM. Testing for dihydropyrimidine dehydrogenase deficiency to individualize 5-fluorouracil therapy. Cancers. 2022;14:3207.
- Wigle, TJ, Povitz, BL, Medwid, S, et al. Impact of pretreatment dihydropyrimidine dehydrogenase genotype-guided fluoropyrimidine dosing on chemotherapy associated adverse events. Clin Transl Sci. 2021;14:1338-1348.
- Hertz, DL. Assessment of the clinical utility pretreatment DPYD testing for patients receiving fluoropyrimidine chemotherapy. J Clin Oncol. 2022;40:3882-3892.
- Luenburg, CATC, van der Wouden, CH, Mijenhuis, M, et al. Dutch Pharmacogenetics Working Group (DPWG) guidelines for the gene-drug interaction of DPYD and fluoropyrimidines. Eur J Hum Genet.2020;28:508-517.
- Caudle, KE, Thorn, CF, Klein, TE, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing. Clin Pharmacol Ther. 2013;94:640-645.
- Amstutz, U, Henricks, LM, Offer, SM, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for dihydropyrimidine dehydrogenase geneotype amd fluororpyrimidine dosing: 2017 update. Clin Pharmacol Ther. 2018;103:210-216.
