DPD Deficiency

Definition: from DPD Wiki "...Dihydropyrimidine dehydrogenase deficiency (DPD deficiency) is an autosomal recessive[1] metabolic disorder in which there is absent or significantly decreased activity of dihydropyrimidine dehydrogenase, an enzyme involved in the metabolism of uracil and thymine."

When a DPD person is treated with 5-FU, the drug’s normal life span in the body is increased greatly.  Instead of being metabolized and being expelled, it continues to do its primary job: kill cells.  Depending on the level of DPD deficiency and the amount of 5-FU administered, it will lead to great suffering, long term disabilities and even death.

DPD Deficiency was first identified as a genetic issue around 1985.  Genetic research has produced a large amount of information regarding both the genetic mutation and its relationship to 5-FU toxicity. The different studies may vary in percentages of occurrence, origins of the mutation or method of identification. They do however agree on one thing: PRETESTING FOR DPD DEFICIENCY IS RECOMMENDED BEFORE TREATMENT WITH ANY 5-FU BASED DRUG.

The most commonly referenced percentage of partial DPD Deficiency in the population is eight percent. While studies differ in race, it appears to occur more often in women
Milano et al. (1999).

It is listed as a
rare disease (affects under two hundred thousand people) by the Office of Rare Diseases, National Institutes of Health. BUT... The mortality rate is nearly 100% when a person is completely DPD Deficient. DPD Deficiency is extremely rare. The second statement is not very comforting given the potential outcome of the first, is it?

Statistics can be misleading.  One common reference is that 3-5% of the population suffers DPD Deficiency.   Other studies state up to thirty percent of patients tested exhibit DPD Deficiency.  The lower percentage seems to be based on the small amount of the more severe cases documented.  The later is based on control study groups and is all inclusive:  any level of deficiency is counted.  The mortality rate of those with more severe deficiency is fairly consistent in all studies at 30 percent.

As you learn more about the risk, which would you rather hear from your doctor?  “It's not that big a concern, let’s proceed.”  OR  “There is a potential risk you should be thoroughly aware of and tests are available to ease your concerns.”

Remember: According to the NIH, 1,300 are killed annually by 5-fu toxicity.
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Fluorouracil was first synthesized and marketed in 1957. Its toxicity has been documented for decades as noted in this abstract: 5-Fluorouracil in Cancer: An Improved Regimen published in August, 1970.
It is in the antimetabolite family of drugs. It attacks rapidly dividing cells but does affect the whole system. Since cells of the digestive tract and mucus membranes divide rapidly, they are heavily affected as well. Under normal conditions, Fluorouracil's half-life in the body is ten to twenty minutes.

Used to Treat
Colon Cancer | Gastrointestinal Cancers: Anal; Esophageal; Pancreatic; Gastric | Inflammatory Breast Cancer | Ovarian | Bowel Cancer (as a key component of Tegafur-uracil
) | Actinic Keratoses | Basal Cell Carcinomas | Opthalmic Surgery | Squamous Cell Carcinoma of the Head and Neck | Genital Warts (NOT FDA approved use, considered an “unlabeled use”) | Cervical Dysplasia (also an unlabeled use???) there are reported uses of 5-fu in cosmetic, “anti aging” treatments, wrinkle reduction, etc as well.
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Trade Names Every link below lists DPD Deficiency and/or 5-fu toxicity. Note how severe toxicity information has little prominence on the commercial links
Fluorouracil 5-Fu 23 products listed. 21 made in China, 2 in India | Adrucil Links to TEVA See MSDA and Prescribing Information | Carac See "prescribing information" link @ bottom of page | Efudex DPD risks, information hidden via link @ bottom of page(opens new page) | Fluoroplex | Xeloda |Capecitabine

Other (foreign) Names: Provided in case you happen to be subscribed these. Same warnings apply as they are 5-FU based.
AccuSite | Actino-Hermal | Arumel | Efurix | Fiverocil | Flurablastin | Fluracedyl | Fluracil | Fluril | Fluroblastin | Flurox | Ribofluor | Timazin
Methods of use
Injection | Infusion | Topically in cream form | Orally

ABOUT.COM sheds some light on a question I have had: does body fat make a difference on the dosage used? It would appear so in this study.

Side Effects
Visit Patientsville.com for starters. Heavily ad based site but has many patient reported cases of 5-FU toxicity. Notable on the upper left of the page are some stats: 1628 adverse reaction reports on the site, 236 ended in death. Hospitalization: 1117. Fourteen percent mortality rate, sixty-eight percent reporting hospitalization. Like the odds?

Hand-Foot Syndrome
Mucositis throughout the entire gastrointestinal tract. The onset of this presented as a sore, very sore throat.
Cognitive Side Effects One detailed article. Thanks reader for sharing this. I was saddened recently when my son had the realization that had his mother lived, she would have likely had a very poor lifestyle due to issues such as this.
Chemotherapy Induced Diarrhea More details here or search the topic.

Some obvious early side effects we experienced: Reddening of the face, chest and shoulders. Almost to a dark purple in places. Pores began turning red then darkening to almost purple-resembling acne or pox of some sort. The skin on the face and hands began to become dry and flaky as if chemically burned. Skin, especially the face and hands became easily irritated, very much so when using moisturizing creams to soothe. Burning sensation on these affected areas. Sore, swollen throat which became so bad it was unbearable to eat, talk or swallow anything. The mucositis started with an irritation of the sinuses and throat then affected the entire system. Disorientation and balance were impaired within several days. Someday, I’ll be able to objectively detail this experience.

Tracking fatalities using death certificate data would prove nearly impossible as it appears from our experience that the toxicity is not listed for cause. The cause of death is most likely the problems caused by toxicity: Thrombocytopenia; Septicemia; Cardiac Arrest, etc.

Fluorouracil Use & Pregnancy:
Detailed article on Drugsafetysite.com

1,300 fatalities per year.
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Cancercompass Discussion: Antidote for Fluorouracil Overdose A reader mentioned this to me. I have not heard of this before. There are several links to it on Google. Hopefully it works and becomes more readily available. New York State Poison Center's News Release for the drug. (opens PDF)

ANTIDOTE UPDATE: again, from www.fu-fda.com. More promising details on an antidote being effective in 5-fu overdose here.

Wikipedia Chemocare.com National Cancer Institute FDA

American Society of Clinical Oncology (ASCO) Per their web site: ”ASCO is the world’s leading professional organization representing physicians who treat people with cancer”  Enter “DPD Deficiency” (with or without “toxicity”) in their search box for a very thorough return of information.  Relevant information by a professional publication readily available to your healthcare professional.
Cancercompass.com A great resource for information on DPD Deficiency.  Their 5-FU Toxicity message board seems to be the most thorough spot for patient and caregiver experiences. This is where I first learned about this condition.  Thanks Cancercompass.com for the information.
DPD Deficiency Wiki Wikipedia article explaining DPD Deficiency.

Cancer Treatment "Business" Websites Not Sharing The WHOLE STORY
Wouldn't you think sites like these should be the absolute best source for treatment education? I do. My purpose in the following links is to bring light to how often one may get a “feel-good” story without the WHOLE STORY being told/sold.
US ONCOLOGY I found NOTHING using their search box or reading the side effects page regarding the potentially fatal risk of 5-FU Toxicity.
Cancer Care Centers Of South Texas The center that treated my wife. There is absolutely nothing on their public website regarding 5-FU Toxicity of DPD Deficiency. They do however provide the definition of DECEASED...Dead. Ironic.
Cancer Treatment Centers of America Fluorouracil is found in their search. Nothing on its risks and nothing found for DPD Deficiency.
M.D. Anderson Center Almost! At least "DPD Deficiency" turns up results in their search box.
American Cancer Society Yea! Sort of. They have the typical message but at least here's a place that has it: "TELL YOUR DOCTOR IF..."
Cancer Therapy and Research Center @ UTHSC, San Antonio Nothing found on DPD Deficiency or Fluorouracil
Fred Hutchinson Cancer Research Center Nothing found on their site search. Fluorouracil toxicity is mentioned in reference to treatment studies. Still no information for the inquiring potential patient.
Fluorouracil use in plastic surgery. Again, As a matter of contrast, here is a blog that mentions Fluorouracil frequently but I can still find no reference to 5-FU toxicity or DPD Deficiency. THE BLOG I pointed this out to the Blog’s author on 30 November, 2010.

Popular Cancer Awareness Websites Not Discussing DPD Deficiency or Fluorouracil Toxicity:
I discovered the Livestrong© site mentions the use of Fluorouracil. I could not find the “whole story” of the potential dangers of the drug and DPD. I notified them both in message and email on 11/6/10. Hope to hear back from them and see a more clear reference to the side effects. No reply, 21 November.
Susan Komen© I searched for nearly an hour and found no clear mention or referrals for these topics. I emailed their website suggestion contact on 12 November. No reply yet, 21 November.
I stumbled upon this
article from The University of Michigan Health System. It discusses 5-FU use to improve the appearance of againg skin. Emailed contact on 29 November to make them aware the article lacks information for 5-FU toxicity.
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