www.know_the_risk_of_5fu_chemotherapy.com

ask about your risk of VERY serious side effects before starting 5-FU Chemotherapy


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Date of latest revision: 4 Dec 2019

Test Types

 

  • Pre-screening: There are two category types: (1) Genotype, and (2) Phenotype.
    • Genotype: this test looks for variations in the DPYD gene. There are some well known variations that lead to reduced DPD activity in patients., and therefore greater risks in the course of treatment, though not all of the possible variations have been discovered.
    • Phenotype: this blood test measures the ratio of uracil to dihydrouracil to determine a patients DPD enzyme level activity. This type of test will show patients with a genetic condition AND patients who, may for other reasons, be at significant risk because of a reduced DPD enzyme level.  This type of test is currently used successfully in France and has become the nations standard of care.
    • Combined test:  This test uses both the geno/phenotype method (see ODPM below).
  • Treatment monitoring: these tests, typically phenotype, are may be used after the start of chemotherapy and serve to guide dose adjustments in future treatments (see for example, My5FU below).

My recommendation is to certainly start with pre-screening followed by treatment monitoring if you are found to have a reduced DPD level.

Testing Services  -- Use one of these before starting treatment

 

Disclaimer:  these testing services are listed in random order and this website has no financial interests in any of these services. Today the cost of the tests ranges from $250 to $500 and those costs will likely converge as testing is used more frequently and as the competition among labs increases.

 

OneOme

This lab performs genetic tests to help guide physicians to prescribe the correct course of treatment. Included in their genetic test, a cheek swab, is a test of the DPYD gene for DPD deficiency. The cost of the test is currently $250.00, which may or may not be covered by your health insurance provider; while that cost may be a pinch for you, it will be a small consideration if you have to later pay expenses associated with severe toxicity.

 

For more info, go to https://oneome.com/

 

Quest Diagnostics

Among the many tests available at Quest sites is a genetic test for DPD deficiency. This test screens for the most common genetic variants that may put a patient at risk -- some oncologists may argue that the test fails to cover all possible variants but this is better than no pre-screening at all.  You will need your physician to authorize this test.

 

The current cost of this test is $479.19 (Nov 2019); you may expect results within 1 week after the sample is received by Quest.

 

For more information see:

https://testdirectory.questdiagnostics.com/test/test-detail/15538/dihydropyrimidine-dehydrogenase-dpd-gene-mutation-analysis?p=r&q=DPD%20deficiency&cc=MASTER

 

Mayo Clinic

 

 

For more information see:

https://www.mayocliniclabs.com/test-catalog/Clinical+and+Interpretive/65213

 

Genelex

 

For more information see:

https://www.genelex.com/test-menu/dpyd/

 

ARUP Laboratories

 

For more information see:

https://ltd.aruplab.com/Tests/Pub/2012166

 

It is interesting to note the limitations specified by ARUP Labs for it highlights that non-genetic factors may also affect DPD activity and treatment outcomes -- so be sure your oncologist and you stay vigilant in monitoring your symptoms. This limitation also suggests a more comprehensive test, such as offered in France by ODPM (see below), and the phenotype tests performed in French hospitals have great value.

 

Saladax Laboratories -- My5FU Test

 

This test may be used to monitor fluorouracil levels in the blood stream during the course of treatment. It is not intended to be used for pre-screening. For more information see: https://mycaretests.com/oncology/products/

 

Onco Drug Personalized Medicine (ODPM)

 

This French company offers a more comprehensive test as it conducts both genotyping and phenotyping (for genetic factors that may compromise the DPD enzyme level and the actual DPD enzyme level in the blood sample).  The company also provides instructions to oncologists to guide treatment depending on the patient's test results.

 

For more information see:

https://www.odpm.fr/en/Patient/Personalized-Chemotherapy-Treatment

 

You may also follow ODPM on Facebook and Twitter.

 

Oxford Cancer Biomarkers (United Kingdom)

 

This British company offers genotyping called ToxNav. It's website states that: "ToxNav, a CE marked test, is designed to identify patients most at risk from severe drug reactions before treatment with 5FU/capacitabine. By detecting the presence of 19 genotypic variants associated with adverse toxicity, you can avoid potentially life-threatening toxicity in your patients and reduce costs associated with its consequences."

 

For more information see: https://oxfordbio.com/product/toxnav/

 

Sonic Genetics (based in Australia)

 

For more information see:

https://www.sonicgenetics.com.au/tests/dpyd-screen/

 

 

ANTIDOTE -- Vistogard

If you suffer early onset toxicity (see Warning Signs...) , you must act FAST and report your symptoms to your oncologist. Do NOT accept a summary dismissal of your concerns: the antidote must be administered within 96 hours of your last treatment to be effective.

 

This is a costly antidote but it can prevent fatalities and shorten lengthy and costly hospital stays.

 

For more information see:

https://www.vistogard.com/TrueCostOfToxicity

 

 

Organizations Offering Information and Support for Patients

 

American Cancer Society

 

Find Support and Treatment:  http://www.cancer.org/treatment/index

 

Guide to Cancer Drugs, specifically 5-FU: http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/fluorouracil

 

This page encourages you to discuss conditions with your doctor before starting treatment and here is what is said about DPD deficiency:

 

"If you have ever been told you have a dihydropyrimidine dehydrogenase (DPD) deficiency. DPD is an enzyme the body uses to process this drug. This inborn genetic abnormality can cause extreme side effects if you use 5-FU (even on your skin) or capecitabine. DPD deficiency can be present without symptoms, so you may not know you have it until you get one of these drugs or are tested for it."

 

Pasted from <http://www.cancer.org/treatment/treatmentsandsideeffects/guidetocancerdrugs/fluorouracil>

 

This page also lists possible side effects for which you should be alert and not bashful about discussing with your doctor at the first sign of trouble.  If you think your reaction is not normal, do not ignore the problem.

 

Colon Cancer Alliance  www.ccalliance.org

Enter 5-FU into the website's global search tool to find info on topics Chemotherapy and Biologics (here it identifies the drugs and the side effects but it does not discuss the probability of severe toxic reactions), Treatment Side Effects (no grading of the toxic effects), and Personal Stories among other related topics.

 

Live Strong   www.livestrong.org

 

Good support organization to help prepare for treatment but lacks specifics for dealing with individual treatment regimens such as 5-FU.

 

StrongMom  https://www.strongmom.org/

 

"Our mission is to provide financial support for the Prettitore Family and to raise awareness of DPD deficiency while striving to make patient testing for DPD Deficiency a requirement prior to 5-FU based chemotherapy treatments."

 

Professional and Governmental Organizations Guiding Treatment

 

Clinical Pharmacogenetics Implementation Consortium (CPIC)

 

"CPIC guidelines are designed to help clinicians understand HOW available genetic test results should be used to optimize drug therapy, rather than WHETHER tests should be ordered."

 

The CPIC recommends a reduction by 50% or greater of fluorouracil or capecitabine when genetic test results find a patient at risk of severe toxicity.  For more information, see: https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/

 

US Food and Drug Administration (FDA)

 

The FDA publishes label warnings for drugs used in chemotherapy treatments.  

 

You can find the package insert Fluorouracil at:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/012209s040lbl.pdf

Key points include:

"5 WARNINGS AND PRECAUTIONS

5.1 Increased Risk of Serious or Fatal Adverse Reactions in Patients with Low or Absent Dipyrimidine Dehydrogenase (DPD) Activity Based on postmarketing reports, patients with certain homozygous or certain compound heterozygous mutations in the DPD gene that result in complete or near complete absence of DPD activity are at increased risk for acute early-onset of toxicity and severe, life-threatening, or fatal adverse reactions caused by fluorouracil (e.g., mucositis, diarrhea, neutropenia, and neurotoxicity). Patients with partial DPD activity may also have increased risk of severe, life-threatening, or fatal adverse reactions caused by fluorouracil. Withhold or permanently discontinue fluorouracil based on clinical assessment of the onset, duration and severity of the observed toxicities in patients with evidence of acute early-onset or unusually severe toxicity, which may indicate near complete or total absence of DPD activity. No fluorouracil dose has been proven safe for patients with complete absence of DPD activity. There is insufficient data to recommend a specific dose in patients with partial DPD activity as measured by any specific test."

 

"17 PATIENT COUNSELING INFORMATION

Advise: Patients to notify their healthcare provider if they have a known DPD deficiency. Advise patients if they have complete or near complete absence of DPD activity, they are at an increased risk of severe and life-threatening mucositis, diarrhea, neutropenia and neurotoxicity [see Warnings and Precautions (5.1)]."

 

 

The package insert the FDA requires for Xeloda use contains the following information:

 

Contraindications (in other words, not to be used when the following conditions are known)

• "Dihydropyrimidine dehydrogenase (DPD) deficiency

• Severe Renal Impairment

• Hypersensitivity

 

Warnings and Precautions

• "Diarrhea: May be severe. Interrupt XELODA treatment immediately until diarrhea resolves or decreases to grade 1. Recommend standard antidiarrheal treatments.

• Coagulopathy: May result in bleeding, death. Monitor anticoagulant response (e.g., INR) and adjust anticoagulant dose accordingly.

• Cardiotoxicity: Common in patients with a prior history of coronary artery disease.

• Pregnancy: Can cause fetal harm. Advise women of the potential risk to the fetus.

• Hand-and-Foot Syndrome (Grade 2 or 3): Interrupt XELODA treatment until the event resolves or decreases in intensity.

• Hyperbilirubinemia (Grade 2 to 4): Interrupt XELODA treatment immediately until the hyperbilirubinemia resolves or decreases in intensity.

• Hematologic: Do not treat patients with neutrophil counts <1.5 x 109/L or thrombocyte counts <100 x 109/L. If grade 3-4 neutropenia or thrombocytopenia occurs, stop therapy until condition resolves.

 

Adverse Reactions

"Most common adverse reactions (≥30%) were diarrhea, hand-and-foot syndrome, nausea, vomiting, abdominal pain, fatigue/weakness, and hyperbilirubinemia. Other adverse reactions, including serious adverse reactions, have been reported."

 

 National Comprehensive Cancer Network (NCCN)  http://www.nccn.org/professionals/physician_gls/f_guidelines.asp

 

This site contains guidelines oncologists rely upon to detect and treat all forms of cancer.  The guidelines for treating colon, rectal, anal, breast, head/neck cancers do not contain warnings concerning the risk of treating DPD deficient patients with 5-FU -- see also Petitions.