It is a year since my dear Mum died after being poisoned by 5-Fu. They'd caught bowel cancer early after she went to her GP with problems. He was straight forward and said he thought it was bowel cancer but would have to refer Mum for confirmation.
Tests confirmed bowel cancer which hadn't spread. Chemo for a month, then operate to take out the offending piece, rejoin and all would be well. Pretty standard procedure with good prospects.
Day 3 of oral chemo, Mum suffered a chronic reaction to 5-Fu. They first said she was diabetic which in my opinion was a red herring. Her sugar level rocketed because she was fighting a poison. They shoved her on the diabetic ward which is when I went to see her; the last time I saw Mum as Mum, but bright red in the face, her mouth and tongue beetroot red. Her throat was raw, she was in severe pain in her abdomen. Something was not right and it wasn't diabetes.
Blood infection followed two days later, moved to intensive care (ICU) where they fought to keep her organs going for a few days. Here, the ICU consultant diagnosed DPD deficiency, which by then was too late. Two days later he declared there was nothing more he could do, and turned off machines for Mum's sake. Mummy died 40 minutes later, it was truly horrible, horrible, horrible, horrible to witness, I cannot and won't describe watching my Mum die. It still haunts me.
We met her oncologist consultant a few days later. He was very shifty, he knew of DPD deficiency, but had never seen it in any of his patients in 25 years of practice. He said it's such a small risk, they don't test for it, at least not in Cheltenham General Hospital, UK. Maybe in Oxford, UK, if not you're talking USA. But he claimed she was diabetic which was not known; Mum was 73, if she was diabetic it would have been known years ago, even as type 2. I consider this is a get out - I don't think Mum was diabetic. With the number of tests she has as part of her cancer investigation and treatment plan, diabetes would probably have been picked up.
Mum died with my Dad, sister and me with her.
A year on, Dad thinks she knew we were there and that she also knew she wouldn't make it because of this stuff she had taken per the prescription. I hope she knew we were with her.
It's a known risk, as her consultant admitted. Are there statistics on DPD mortality within the UK? Any help would be welcome.
Mum's terrible sequence of events is almost identical to Cheryl's and the photo dated 27 Dec.
Graham Hindley
London, UK
“I was diagnosed with Stage I breast cancer, I was 40 years old. The treatment plan was routine, lumpectomy, chemotherapy and then radiation therapy followed by oral medication for 5-years. On July 15, 2005 I received my first round of chemotherapy, 5-FU, Epirubicin and Cytoxan. On July 27, 2005, 12-days post chemo, I was admitted to the ICU with what was later determined to be severe 5-FU toxicity. The days following chemo I was experiencing most of the side effects I had been told about. However, they continued to get worse each day rather than subside. On the morning of July 27, 2005, I was unable to swallow, due to the severe pain in my mouth, swallowing my saliva felt as if I was swallowing razor blades. Extremely weak, with diarrhea, abdominal pain, and a rash, I was taken to the Cancer Center to see my Oncologist. I was then directly admitted to the ICU for 13-days. I was diagnosed with: fever, neutropenia, severe mucositis, odynophagia, dysphagia, nausea, vomiting, weight loss, generalized abdominal pain with dyspepsia, severe diarrhea, generalized weakness and a diffuse macular erythematous rash later diagnosed as hand/foot syndrome . Unable to tolerate food or fluids, I was placed on TPN and lipids to maintain nutrition and hydration, and antibiotics for the fever. I received 2-units of packed cells for symptomatic anemia as well as multiple transfusions of platelets for severe thrombocytopenia. Six sets of blood cultures were negative, stools checked for c-diff were negative, urine cultures negative. I was not lucid most of the first 5-days of my hospital stay. With family at my bedside around the clock, they were told I may not make it and asked if they would like to speak to the Social Worker to assist with making arrangements should I not survive. On July 28, 2005 the following test was ordered: Dihydropyrimidine dehydrogenase (DPD) assay. I was then diagnosed with 5-FU toxicity secondary to DPD deficiency. I was told by my physician that this is very rare and only occurs in 2 in a million people. The doctors told my family the only treatment was to treat the symptoms and they were doing everything they could. When asked why I was not tested for this my family was told it is not the standard of practice to test for this deficiency, because it is so rare. I did improve and was discharged home after 13-days in the ICU. Upon discharge I was able to walk 25-50 feet with assistance, I was still very weak and began exhibiting other side effects, expressive aphasia, unsteady gait and leaning toward the right side, and I had very poor fine motor skills in my hand which I realized when I went to write a note and could hardly write. My first follow-up with the oncologist was one week after discharge. I explained my symptoms and a MRI of the brain was ordered. The results of the MRI identified an area on the corpus callosm 5mm. The Neurologist sent me to the Neurosurgeon who decided to watch the area and follow-up with another MRI in one month. More testing was ordered to try to determine what treatment was to follow. A spinal tap ruled out demyelinating disease, a second MRI showed some improvement in the area. Unable to explain this, my Neurologist found a study involving patients with 5FU toxicity, and the study was small only 5 or 6 patients my Neurologist explained because most people don’t survive. However, in this study it was noted following the event, abnormal brain MRIs were noted, and eventually resolved without treatment. This was good news for me. I resumed my chemotherapy (not on 5FU), and continued to get brain MRIs monthly, and the area dissipated after 6-months. I finished my chemotherapy in December 2005, and my radiation therapy in March 2006. Here I am 5-years later, and very grateful to be alive. I thank god and the many prayers for getting me through this. I have never returned to my old self. I suffer from fatigue, chronic pain, and still have trouble remembering at times. One might say this is all part of the aging process, however I truly believe this is all residual effects of the 5FU toxicity.”
~Mary R. 45-years old
To whom it may be concern
DPD Partial/Complete Deficiency – Important!
I’m active for the benefit of 5% of the population, who is suffering of partial/complete DPD (Dihydro Pyrimidine Dehydrogenase) enzyme deficiency, following suffering of serious toxicity, entailed by topical use of Verrumal Solution, which contains 0.5% of 5-FU (Fluorouracil), for treating a verruca in my foot.
It will be noted that the leaflet to the patient did not include any warning or note, as for DPD enzyme partial/complete deficiency, nor as for the catabolic path-way of the 5-FU. It will be also noted that the dermatologist reassured me that this drug is considered as safe for many years.
Adverse effects included acute back pain for 3 weeks, changes to nails (chipped, brittle and fall out), loss of appetite, loss of weight and bone marrow suppression of the White row IAW the 5-FU well known adverse effect on it.
Additional adverse effects were experienced during the second week after stop using the Verrumal and included: blurred vision, dizziness and acute weakness and tiredness.
All adverse effects vanished a month after stop using the Verrumal.
I’m very grateful to my haematologist at the hospital, who notified me, that it’s likely that the bone marrow suppression is related to the 5-FU active ingredient, contained in the Verrumal, and that therefore my chances for full recovery are high.
After my recovery, I sourced relevant publications, read them and have reached the conclusion that it’s likely that I’m suffering of partial/complete DPD enzyme deficiency. A DPD enzyme activity test, which I initiated, supported my assumption.
As such I would like to bring to your attention the following:
1. Screening for partial/complete DPD enzyme deficiency should be a pre-requisite before start using any drug that contains 5-FU, including drugs for topical use, no matter how low the 5-FU concentration is (e.g. Verrumal Solution 0.5%!).
2. To the best of my knowledge, the correct test to conclude partial/complete DPD enzyme deficiency is a metabolic one, which measures the activity of the DPD enzyme in the blood.
This test can be executed at several laboratories including:
1) Lab. Genetic Metabolic Diseases, Laboratory Division, Emma Children’s Hospital AMC, university of Amsterdam, Amsterdam, Holland (http://www.labgmd.nl ).
POC - Prof. dr. R.J.A. Wanders, gmz_enzm@amc.nl, Tel. +31 20 5662026, +31 20 5665393, Fax +31 20 6962596
2) Laboratoire d’Oncopharmacologie et Pharmacoge’ne’tique, Centr Re’ginal de rechereche INSERM, Centre Re’gional de Lutte Contre le Cancer Paul Papin, universite’ angers, Angers, France (https://www.centrepaulpapin.org ).
POC – Prof.. A. Morel, Dr. M. Boisdron-celle, a.morel@unimedia.fr , m.boisdron@unimedia.fr , Tel. + 33 02 - 41352717, +33 06 80407345, Fax +33 02 41483190
3. To the best of my knowledge, the TheraGuide 5-FUTM , executed by Myriad Genetic Laboratories, Inc. in the USA, does not measure the activity of the DPD enzyme, but executes sequencing of the DPYD gene for possible detection of only three (3) known mutations (IVS14 + 1 G>A, D949V, 1560S) plus variants, which their exact identification is not specified in the document: TheraGuide 5-FU TM Technical Specifications Myriad Genetic Laboratories, Inc. Updated: 12 July 2007 – http://www.myriad.com/lib/technical-specifications/TheraGuide-5-FU-Technical-Specifications%20web%20version.pdf
4. To the best of my knowledge, there are at least 23 known and unquestionable mutations in the DPYD gene, proved to be related to partial/complete DPD enzyme deficiency (See the list below).
5. To the best of my knowledge, a complete Genotype of the DPYD gene that ends without detecting any mutation, does not rule out the possibility of partial/complete DPD enzyme deficiency, because the root of the problem may reside in the phenotype of this gene.
6. To the best of my knowledge, it hasn’t been approved yet beyond any doubt, that the DPYD is the only gene that is related to the activity of the DPD enzyme.
7. The Verrumal leaflets for the doctor and for the patient have been amended both in Germany and in Israel, upon my request. However, to the best of my knowledge, my request from The Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) to enforce the manufacturer to amend all Verrumal leaflets distributed out of Germany as well, was not met.
8. In light of all mentioned above, it is highly recommend to take an action world-wide and negotiate with the relevant governmental health authorities as well as with world health organizations, in-order to make sure that drugs for which DPD enzyme is included in the catabolic path-way, won’t be prescribed, unless the enzyme activity in the blood has been already tested and the possibility for partial/complete DPD deficiency has been ruled-out.
DPYD Gene – Mutations List
1. Manufactured by Hermann GmbH & Co., D21565 Reinbeck/Hamburg, Germany
2. Received kindly from Prof.. A. Morel & Dr. M. Boisdron-celle, Laboratoire d’Oncopharmacologie et Pharmacoge’ne’tique, Centr Re’ginal de rechereche INSERM, Centre Re’gional de Lutte Contre le Cancer Paul Papin, universite’ angers, Angers, France
~ Adit M., Israel
Efudex Treatment
“Hello my name is Carol W., I started using FU-5 cream on December 13th.
I used this cream on my chest area to remove precancerous spots caused by
the sun. On December 18th I became very sick. I ran a fever of 102.3 for
about 3 days, severe diarrhea 15-20 times a day for several days, body aches
and chills.
My life has not been the same since December 18th 2010. I have had problems
in the past with my digestive system , it has always been hard for me to
digested a lot of different food items. I had also recently had c-diff
colitis November 5th 2010 and it reoccurred again later that month which I
think was originally caused by over use of antibiotics. I was able to get
better with c-diff usually with in a few days .
This last attack seems very different. I have been on Vancocin 125mg 4 times
a day since 12-20-2010 which now is about 6 weeks. I had a colon test on
the 20th that showed colitis but the bioscopy said unknown colitis on this
test.
I am getting more test Tuesday 2-1-11 and I will let you know what the
results are.
Thanks”
~Carol W.
“My partner died of 5FU toxicity on 8th August this year. He was diagnosed with small bowel cancer in May - the tumor was removed surgically. Oncology prescribed follow up chemotherapy (oxipilatin and capacitibane) to prevent reoccurrence. We were told of the general side effects, but neither of us had heard of DPD deficiency and were unaware that chemotherapy can kill. Before treatment Rick was a healthy (probably cancer free)47 year old. He died after suffering horrific side effects just 4 weeks after his first round of chemo. He leaves 3 children aged 16, 14 and 3. I can't understand why there is no testing for DPD prior to treatment, and just hope that raising awareness may help others in the future.”
~Stephanie 19 Dec, 2010
Another sad and unnecessary loss to the lack of standardized testing for DPD Deficiency. Please put yourself in this husband's shoes. "Though she lives on through her children and grandchildren, this site is an attempt to help Cheryl's death, not be so meaningless, as it seems at times to be to me."
I have recently been in contact with a man who is suffering from severe after-effects of a very small amount of Efudex topical cream. Visit his page from the link below. Follow his story. Its hard to imagine living each day with those you trust to treat and do you no harm in reality be clueless to your plight.
Fluorouracil 5% cream
"I had one dose of cream chemo for an abnormal pap smear. I only had vain 1...it wasn't even pre-cancer in April. I am now disabled and had to give up my job of 24 years. I live in excruciating pain. It is not approved for usage by the FDA for this purpose."
~Marianne A. 10 Nov, 2010
Posted on the old Forum April 2009 via email:
I am sorry to hear about Cheryl. To lose someone because of a treatment that was supposed to save lives is devastating.
In 2005, my dad also died after his first round of 5fu. My father had been diagnosed with color rectal cancer with a 75% chance of recovery without chemo. But on the advice of the oncologist went ahead with the treatment. Never was there a discussion about the possible adverse reactions of 5fu if there was an enzyme deficiency.
Within a week Dad was in the hospital with extreme mouth sores, low white blood count, redness and tenderness of skin and difficulty breathing. Within a week he was on life support, with a big purple blotch covering most of his forehead and nose, as his organs were beginning to shut down. Approximately 3 weeks after his first round of chemo we made the excruciating decision to take Dad off life support where he passed away shortly after.
The oncologist, unfortunately, was like a deer in head lights. Not having a clue what to do. Through our own research we found out about DPD deficiency and learnt very quickly that there was not much that could be done to counteract the drug. And although we never had an autopsy performed or any other testing done we do believe that most definitely Dad had this enzyme deficiency.
I filed a drug adverse reaction report with Health Canada but I didn't hear anything back from them. It wasn't until the lady in Edmonton died of her overdose of chemo that I contacted the Institute for the safe practice of medicine, who were conducting the investigation into her death, that I finally got someone to listen to my story. After giving them full details of my dad's death they investigated the risks of 5fu. And although it is not known whether this lady had an enzyme deficiency that compounded her overdose of the chemo or just passed away from the overdose, the report does briefly go on to mention the risks of 5fu and the genetic component to it as well.
Following this report, ISMP also sent a note to Health Canada to ask them to "review the drug and possibility to request the manufacturer to add information about DPD deficiency and the increased sensitivity to fluorouracil" At the time, Ontario and BC were the only 2 Canadian provinces that provided this information. I believe all provinces now need to provide this information in the brochure but I am not 100% sure of this.
But still there is no testing. And the only way to get tested for the deficiency is to get it done in the United States. I have no problem doing this for myself or my family. But I do worry about all the people who aren't even aware of this drug reaction, who like us, only find out after it is too late.
So thank you for the website and a hopeful start to getting the necessary information out to people who need it. It is my hope that if the United States makes testing more commonplace, than the availability will be easier in Canada.
I like to think that my dad's death was not in vain and that I will be able to change the procedure to help others in the future. And hopefully I can be some help to you in the future.
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Posted on the old Forum March, 2009 via email:
The following story was provided by a family member of a cancer patient who succumbed to either 5-FU toxicity/overdose or DPD Deficiency.
...Hi,
My family's story parallels that of your family documented on the website. I could provide more details if needed.
My mother, age 74 was diagnosed with an anal squamous cell carcinoma in October/November 2008, size of a quarter. Otherwise she was strong and in excellent health, working most days as a teacher. She had a minor surgery (one night in the hospital) in November to remove the carcinoma, and despite there seemed no lymph involvement was recommended to have a precautionary six-week course of 5FU and radiation. Radiation five days per week, and five-day infusions of 5FU in weeks one and four. I think we all believed the probability of a completely successful cure (no return of the cancer) to be in the neighborhood of 85%.
She started the radiation and 5FU (carrying an IV bag of 5FU in a purse, routed to her arm) on Monday, January 19. She received daily radiation treatments. She told us after four days "this is a strong dose" and that she was feeling bad. The fourth day Thursday late evening she passed out in the bathroom at home and turned white. An ambulance took her to the hospital where she worsened steadily over three weeks and passed away on February 9, some details of which are following.
The radiation was skipped on the day five (first full day in hospital) due to logistics with her hospital admission. In the hospital, the 5FU infusion was continued through Saturday afternoon (day six) as she and we considered this was the path for avoiding the growth of the cancer. She received radiation in the hospital on Monday through Wednesday days 8, 9, and 10, when her burns, pain, and overall state of health prohibited any more radiation. I believe the initial treatment in the hospital was an additional IV for dehydration and sustaining nutrients.
Over three weeks the agonizing symptoms worsened progressively from face hand and mouth sores to body sores, to inflammation of her entire GI tract, to swelling of arms abdomen and legs, to low white cell count (the condition neutropenia kept her isolated in the hospital), to intense pain from burns inside and out exacerbated by the continuous diarrhea, to inability to speak, to hair loss, to mental slowness, to drooping face, to labored breathing and complete non responsiveness. She had a few spoonfuls of ice tea and chicken broth on the days leading up to January 31. She had a few spoonfuls of egg custard (her request) on Feb. 4. She neither ate nor drank after that, relying solely on the nutrient IV and occasionally a touch of ice chips. She received diuretics to lower the swelling. She had one or more CT scans to rule out clots and infection. Occasional treatment with platelet transfusion had begun on February 1. She was given continuous access to morphine starting around February 1. She could speak only a few words on February 5 and 6. Her breathing was labored on February 7. She was moved to the ICU on the Saturday evening February 7. She received a ventilator through her nose on February 8 which seemed to give her some relief in a worst condition. She received various injections to raise her blood pressure and regularize her heart beats. She received painful skin cleansing and ointment every few hours. There was much concern for potential infection of the inflamed skin. We were hopeful for several weeks that the white cell count would turn around and the oncologists said it always did. She had an "episode" of seizure or heart arrhythmia in the night of February 8. She was suspected of sepsis, fungus of the brain, and other systemic problems on February 9 in the morning. She received CPR and defibrillation one or more times on February 9 in the afternoon and passed away when the ventilator was withdrawn about 2:00pm in the afternoon. I was fortunate to be holding and talking with her the last two hours.
We first read of DPD deficiency with 5FU on February 5 from the website http://www.cancercompass.com/message-board/message/all,2909,0.htm
We recognized immediately my mother's symptoms from the several discussions. Particularly moving was a lady's description she had survived a similar ordeal only because of her young age forty years. My mother's memorial and burial were February 13 and February 14.
I found your dpd-deficiency website today February 24. Prior to reading the cancercompass website we had understood from the oncologists there may be an enzyme deficiency, that the damage had already been done by the 5FU and that the only way to recovery was to avoid infection, treat the symptoms, and give her love and family support.
We certainly now believe the DPD deficiency pre-tests should be routine, and that symptoms of extreme 5FU toxicity should call for immediate cessation or reduction of the 5FU.
With gratitude and hope this helps others...
"A Son"
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