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

KATHY'S Story

Why you should ask for a DNA test before starting chemotherapy treatments

I became a cancer statistic in 2013 along with more than 1.6 million other Americans.

In short order, I qualified as another statistic: I am one of the 15-30% of cancer patients who experienced a severe and potentially life threatening reaction to the most prevalent anti-cancer chemotherapy treatment prescribed for colon, breast, head and neck cancers.

My toxic reaction, which resulted in a 6 day hospital stay and weeks of recovery, could have been avoided by a readily available DNA test that costs less than $300.  The test screens for specific gene mutations which affect the body’s ability to process and eliminate drugs commonly used for cancer treatment.  As a result, toxins build up and, the body begins to shut down in a debilitating spiral of increasing pain and physical complications.  

After a lengthy article about my experience was reported in The Washington Post,   “Chemotherapy was more than she could endure”, as part of their “medical mystery” series, (May 26, 2015, by Sandra G Boodman)  I received heart breaking emails from families who lost loved ones to the same inherited sensitivity and toxic reaction; they learned too late that these deaths could have been avoided by a readily available DNA screen which alerts oncologists to moderate or completely avoid a drug most commonly known as 5-FU.   

These families also believe that many deaths due to chemo reactions are under reported because it is easier and more politically expedient to do so, even in cases where the cancer had not progressed to a life threatening stage.  One husband informed me he appealed and had the cause of death changed on his wife’s death certificate to state the true cause of her death as a reaction to her chemo treatment.  His four adult children have been tested and found to carry the same gene mutation, so they know they may be adversely impacted by chemo treatments if, God forbid, they are ever diagnosed with cancer.

My message is simple: Ask for a DNA test before beginning treatment with any chemo cocktail that includes fluorouracil or 5F-U, also known as FOLFOX.

                                               The Chemo Reaction from Hell

I was just getting my head around the idea that I was another grim statistic with stage 4 colon and liver cancer when I began chemotherapy treatments with a “chemo cocktail”, which included 5-F-U, the most commonly prescribed anti-cancer treatment.

At the time, I thought I was prepared for the chemo side effects, the nausea, hair loss, exhaustion, change in taste buds, but my reactions were much, much worse than I expected.

After my very first treatment, lab tests indicated that my white blood count plunged so dramatically that my second chemo infusion was canceled and I was prescribed nightly shots directly into my stomach to help my body recover.  I asked my HMO’s medical staff if my reaction was normal; their response was, “Everyone is different.” The chemo treatments continued. My condition worsened.

My hands and feet began to crack and ooze blood.  My gums and nose were bleeding, my mouth so full of sores that I tasted my own blood when I tried to eat.  I could barely get out of bed, which was a problem because I also developed chronic diarrhea and lost 13 pounds of my 130 pounds very quickly.  Sometimes, I just huddled on the bathroom floor with my pillow and blanket because that was the best I could do.

My eyes dried out and my skin, including my ears and eyelids, began to peel and then peel again, like a case of severe sunburn.  My sense of balance was wonky and my legs so weak I had to rest halfway to the kitchen in our small house. I gasped for air at the slightest exertion. This was particularly distressing to me because I was considered fit for my age after years of dance and frequent workouts, with no heart, blood pressure, diabetes or other complications. I was active in water aerobics and yoga and relished daily long walks with my dog, but now even this simple pleasure was denied me.

Finally, and most alarming to my mental state, my eyeballs hurt too much to read, which is my idea of a personal hell which Dante neglected to mention.

I am a woman who managed to carve out a career in very competitive and (then) male dominated environments, but my gritty determination began to falter. I questioned if I could survive what was supposed to cure me.  I raised serious “quality of life” issues with the medical staff. In response, they prescribed a mouthwash for my bleeding mouth.  The nightly stomach shots and the weekly 52 hours of chemo treatments continued.

As my health deteriorated, an emergency trip to the HMO’s urgent care resulted in a diagnosis of the flu, since “that’s what everyone has now”.  A few days later, my condition worsened and a second trip to the HMO urgent care resulted in a blood test which indicated dangerously low levels of white blood cells, potassium and electrolytes. This time, the doctor expressed alarm at my condition, speculated that I had contracted a severe intestinal infection, and said I needed “a complete work up”.  He feared I might have a heart attack, so I was dispatched to the local hospital emergency room via ambulance.

There, a CAT scan indicated that my entire digestive system was “inflamed”, according to the ER triage doctor.  I was admitted and treatment prescribed to curb the suspected infection.  I was attached to a metal tree which dripped a dizzying array of antibiotics, pain killers and other fluids into my veins, all to no avail.  I rocked back and forth in pain that no pain killers could alleviate. Despite tests for infections and various diseases one does not wish to contemplate, the mystery of the cause of my distress continued.  My wonderful, caring nurses hinted, very professionally, but with emphasis, that I should ask for another opinion. 

I demanded a consultation with a gastroenterologist at the hospital.  Finally, she said she found no signs of infection but suggested that my symptoms were the result of an unusually severe reaction to chemo treatments: She changed my treatment completely.  Under her treatment, I gradually improved. I could eat soft foods again and my sense of humor returned. (At one point, I entertained nurses with an impromptu Pink Floyd improvisation, shouting “Pudding!... Will I get my pudding!”  After weeks of chicken broth, a diet of pudding was a delicacy to be savored and I felt less like “one more brick in the wall”.)

However, the cause and effect of the severe reactions remained a concern.  I was scheduled for at least 30 more weekly chemo treatments at the HMO prior to surgery, followed by a continuing regimen of chemo.  I had serious questions about my physical ability and mental will to survive the ordeal and was giving serious thought to which hymns I preferred for my funeral services.

 After 6 days in the hospital I was sent home, although in a much weakened condition, still scheduled for the same chemo regimen at the HMO the following week. 

                   Second Opinion results in DNA test and DPD Deficiency Diagnosis

Fortunately for me, a friend intervened.  She had recently recovered from a similar cancer surgery and months of chemo with no ill effects.  She was alarmed because she had not encountered any one with reactions to chemo drugs such as I experienced.

She made arrangements for my husband and me to meet with her oncologist at Piedmont Hospital in Atlanta.   

One clue to my mysterious reactions was resolved by a review of math calculations; my new oncologist said that I had been receiving at least 30% more of the chemo drugs than indicated by my height, weight and body mass, calculated by “cubing” these factors.    However, my new doctor also suspected something more than a math mistake.   

He ordered a DNA test, and a week later, he explained that I had inherited a gene mutation which affects my ability to process and eliminate 5-F-U, one of the most commonly prescribed chemo cocktails. Mutations in at least three genes are known to cause sensitivity to 5-F-U and this sensitivity is usually associated with DPD deficiency. (The exact medical terminology is a cross word puzzle enthusiast’s dream-dihydropyrimidine dehydrogenase deficiency.)

According to various oncology research articles on the subject, DPD deficiency or 5-F-U sensitivity can be life threatening because the body cannot process certain drugs commonly used in building chemo cocktails, including fluorouracil, or 5-F-U, also known as Folfox.  Many articles advise oncology professionals of symptoms, which include my all too familiar experience with mouth sores, abdominal pain, bleeding, nausea, vomiting and diarrhea, as well as low numbers of white blood cells, which can lead to serious infections.  Furthermore, resulting low numbers of platelets impair blood clotting and can lead to hemorrhage. The toxicity builds until body functions are seriously impaired and can shut down.  According to one Journal article on “Managing Severe Reactions to Chemo Infusions,” the advice to oncology nurses observing such reactions is to “proceed to emergency triage”.

The Genetic Home Reference, published by the National Library of Medicine, explains that DPD deficiency is often found in patients with a history of epilepsy or autism, (I do not have such a condition, nor am I aware of family history of such health issues.)  However, 5-F-U sensitivity can impact a much larger group of individuals, like me, who are unsuspecting carriers of the gene mutation.  I had to break the news of this inherited disorder and the potential implications to my siblings and other family members.  That was a bad day.

This twist of mutated DNA should also be of particular concern to parents and siblings of those with epilepsy or autism who can carry the mutation and not know until treated by chemo and suffer the effects of life threatening toxins their bodies cannot process.

Such mutations affect an estimated 15-30% of cancer patients treated with 5-F-U, according to a recent article with the authoritatively tongue twisting title, “Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive dosing of 5-F-U in patients with digestive cancer”, published in the September, 2015 issue of the British Journal of Clinical Pharmacology.  The article explains that it is a spectrum disorder, ranging from a mild sensitivity, to patient death in about 1% of the cases.

This is not a new phenomenon.  The first description of a fatal outcome in a patient with DPD deficiency was first reported 30 years ago in the New England Journal of Medicine, according to another recent article on the subject, “DPD deficiency in patients treated with fluorouracil”, in the October issue of The Lancet Oncology.

The article discusses the need to address the “upfront detection of DPD deficiency as a means to anticipate and thus prevent life threatening toxicities with fluorouracil drugs.”

 The article reports that, “Despite the amount of clinical evidence on the deleterious effect of DPD deficiency in fluorouracil-treated patients, and the fact that fluorouracil remains the most widely prescribed anti-cancer drug worldwide, DPD testing is still not officially recommended by health agencies and is far from being the standard practice in the clinic.”

In my case, the DNA results were found through a blood test.  However, thanks to friends in health care, I recently toured Medical Diagnostics Laboratories in Covington, Kentucky, for an explanation of their DNA technology testing, which requires only a mouth swab.  Medical Diagnostics Laboratories’ president Brad Denham said their test costs less than $300; my 6 days of hospitalization caused by 5-F-U sensitivity toxic reactions cost more than $30,000, plus continuing prescriptions and medical care.

As a result of the DNA tests, my new oncologist continually reviewed and adjusted my chemo cocktail combinations depending on my physical reactions to the previous week’s dosage.  I began five months of these modified treatments shortly after a successful six hour colon and liver surgery.

As English major, I now boast of my resectioned “semi-colon”.  I‘ve resumed my workouts and aerobics.  My most recent PET scans are encouraging and I refer to myself not as a cancer survivor, but as alumni, with an advanced degree in determination.  I don’t dwell on the possibility that my life expectancy may be affected because I could not tolerate the full dosage of 5 F-U.  The statistics could be worse; I could be dead.

The concluding words of The Lancet Oncology article are noteworthy for their directness and lack of medical jargon: “…It might be time to stop playing Russian roulette when administering standard fluorouracil to patients with cancer.”

Ask for a DNA test for 5-F-U sensitivity if diagnosed with cancer. Your life is potentially at risk from what you think may cure you.  

                                                                         -30-

British Journal of Oncology, Beating the odds: efficacy and toxicity of dihydropyrimidine dehydrogenase-driven adaptive diagnosing of 5-F-U in patients with digestive cancer, September 2015, Dr Joseph Ciccolini and others, Clinical Pharmacokinetics, LaTimone University hospital. Marseille, France.

The Lancet Oncology, DPD deficiency in patients treated with fluorouracil, October 23, 2015, (published in US, Britain, and China) Dr Joseph Ciccolini and others, Clinical Pharmacokinetics, La Timone University Hospital, Marseille France. This article also speaks to the possibility of DPD reactions to capecitabine, a drug commonly prescribed for breast cancer patients, but I was only comfortable relating my personal experience with 5-F-U.

In addition to the Genetic Home Reference cited above, I also found information in articles by Susan Moore, in the Oncology Nursing Forum, published by the Oncology Nursing Society (2009.36 (2) 149-152.

There were several articles I could only access in part, published by W. Vogel in the April 2010 Clinical Journal of Oncology and Diagnostic Assessment in Managing Infusion Reactions, by Elisa Beeze in Clinical Journal of Oncology Nursing.

Kathy Lang Albright