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

Petition to the Public


Contributing to the Body of Learning for the Care of Patients


“This treatment is fairly well tolerated…”  That is what we heard about the 5-fluorouracil (5-FU) chemotherapy treatment prescribed to treat my wife Kathryn’s  late stage colorectal cancer.  Three different cancer centers assured us that she would suffer none of the debilitating side-effects often associated with chemotherapy.   The 5-FU chemotherapy regimen has been used for decades to successfully treat colorectal, head and neck, stomach, and certain breast cancer patients.  Yes, many people tolerate it well. 


Turns out, not everyone does.  Patients, such as Kathryn, with a genetic condition, a dihydropyrimidine dehydrogenase (DPD) deficiency, are unable to metabolize the 5-FU agent.  The DPD enzyme is the single point of failure as it is essential to the metabolizing of the 5-FU to minimize the destruction of healthy cells. Without the enzyme, the 5-FU remains in a patient’s body creating a toxic reaction as the agent continues to destroy good cells at the same rate it attacks cancerous ones. 


The reaction after just one round of the 5-FU may lead to a long hospital stay from a severe toxic reaction or even death.   Within days of her one and only treatment, Kathryn developed a severe mouth infection.  She ate and drank little and needed an IV for hydration within the first week.   Her symptoms built up slowly but persistently until she collapsed and had to be rushed to the hospital on the 9th day after her treatment.  There, in the emergency room, the on call physician from the cancer center concluded that she suffered from the DPD deficiency.


Despite the care administered to her, Kathryn’s condition deteriorated.   She was not producing new white blood cells and was therefore at a high risk of infection.  After one week in the hospital, another physician offered that her body suffered “a house fire” and that it would take time to rebuild.  In Kathryn’s case, however, the fire was not out and it continued to smolder and burn.   Her low white blood cell count, neutropenia, remained a concern but there were other complications. The silent killer was the deterioration of her mucous lining in her digestive and respiratory systems that zapped her strength and never allowed her to recover.  Kathryn passed away after two weeks in the hospital.


It is sad that our community lost a wonderful person full of grace prematurely but what is more sad is that others could suffer a similar fate unless there is widespread adoption of genetic testing for this condition and changes in the monitoring of treatment of patients at risk. 


The health care industry is doing many great things to advance the treatment of cancer.  The Wall Street Journal recently reported advances in isolating different genetic conditions in tumors that allowed physicians to tailor treatment plans.  The health care industry has an opportunity here to tailor a treatment plan by first assessing a patient’s ability to withstand the standard treatment protocol. 


Pre-screening today is not routine nor is it advocated as a prerequisite for 5-FU treatment by the Federal Drug Administration, pharmaceutical companies, the American Cancer Society, or the health insurance industry.  In most cases you cannot identify a person with the DPD deficiency simply by looking at them. Only in severe cases of the deficiency are symptoms evident and most people with this condition appear completely normal until they are treated with 5-FU.  Our children have been tested, a simple blood test, and they know now that they should never receive a 5-FU treatment or they too would suffer a toxic reaction.


Perhaps the incidence of the deficiency is too low to command attention as estimates place it at affecting between only 2 -- 8% of the population yet nearly 15% of patients treated with 5-FU suffer a severe toxic reaction to treatment and the number of deaths each year is estimated to range from 500-1000 in the US.   While the probability of a toxic reaction may be low, the health care industry should have safeguards in place to minimize fatalities.  Pre-screening of patients would appear to be a reasonable and low cost measure though it is not sufficient.  Medical studies show that there is no single test that can identify every patient who may have a DPD deficiency though research continues to piece together this genetic puzzle.   Pre-screening, when combined with tailored doses of 5-Fu and close monitoring of the abilities of patients to metabolize the chemo agent has been shown in medical reports to limit adverse drug reactions.


As she was preparing to start her treatment, Kathryn wrote “I am optimistic and very grateful to all who have traveled this path before me and contributed to the knowledge and experience of those whose vocation it is to heal people like me.  May my experience also contribute to that body of learning.” 


It is time to learn from Kathryn’s case and it is time for a change: care providers should offer, if not insist upon, pre-screening patients for the DPD deficiency before the start of 5-FU chemotherapy.   Pre-screening is not fool proof, so care providers should also consider tailored dosage levels and monitor side effects to detect and quickly treat patients who show early signs of severe toxicity.


A friend of mine suggested that change may come slowly and in the form of one conversation at a time.  I will continue my conversations. 


I hope others join in the conversation and start advising friends and loved ones who are seeking treatment for colorectal, head and neck, stomach, and breast cancer to ask about DPD deficiency screening before their very first 5-FU treatment. 


You may save their life and you may also join in the string of conversations that will change the way the health care industry copes with this condition and improves patient care.


Published in the Battle Creek Enquirer (and picked up by other Gannett newspapers, Dec 2013)