11 January 2020 -- Why Oh Why? Another Mother Lost to 5-FU
This week I learned of another family who lost their mother who suffered a fatal reaction to treatment with 5-FU. In an all too familiar script, the family was stunned to learn there was any chance of severe side effects with this course of treatment which has been used for 50 years. After reading USA Today article concerning Glenn Prettitore's effort to bring about change in the New Jersey legislature, the daughter learned she was another of too many other families who lost loved ones because of the unsafe use of this chemotherapy regimen.
In a case reported earlier, David's Story, his wife succeeded in getting the local paper in Portland OR to report on the actions she is taking following his death. Follow this link to read the story.
Unfortunately the oncologist interviewed in this article chooses not to discuss the risk with her patients because she believes there is not a reliable test nor the method to effectively interpret test results. It is true there is no worldwide standard for test/treatment of DPD deficiency cases, however, there are standards and practices now in place in France and the province of Quebec, Canada.
4 December 2019 -- New Website in the UK
Please see a new website based out of the UK that advocates for pre-screening. The group is aptly named the 5FU Test Alliance. Thanks to Chris Stevens for guiding this initiative. Tragically, Chris lost his wife to 5FU toxicity when she was not tested for DPD deficiency prior to the start of treatment. Chris and the Alliance are lobbying to make pre-screening mandatory in the UK. Best of luck! See the site, which includes videos of personal stories at:
In addition, today you can find the following updates to this site:
22 November 2019 -- Updates to this Site
Please see updates to the following:
- Home page -- added a link to the Help page and referenced the FDA's placing the burden of proof on the patient to advice the oncologist of their DPD deficiency (the FDA has that backward).
- Help page (previously called Resources) -- added information concerning DPYD test services and updated the information on the FDA warning label.
- Warning Signs -- added a link to the Vistogard site that shows early warning signs.
- Personal Stories -- added a link to the Vistogard site that includes a video of people sharing their personal tragedies.
19 November 2019 -- the Story of the Prettitiore Family and a New Test Service
Thanks for the efforts of Glenn Prettitore, husband of the late Kerrie Prettiore, and Lindy Washburn, a New Jersey reporter, the following article made the news in NJ and has been picked up by other news outlets in the USA Today network.
This week I also learned of a laboratory that offers genetic test services to include testing of the DPYD gene. Go to https://oneome.com for instructions on how to order the test. Out of pocket cost (without insurance) is approx $250.00.
15 September 2019 -- Be Vigilant, Do Not Assume
Take nothing for granted when being treated with fluorouracil/fluoropyrimidine chemotherapy products. That's the bottom line of a recently published article in the Pharmacogenomics journal. The journal article, co-authored by Dr. Joseph Ciccolini, reports the case of a patient who died from a toxic reaction after treatment with capecitabine. What is unusual in this case is that the woman previously had been treated with 5-FU with only grade 3 mucositis. Severe toxicity symptoms, however, showed up right away after one treatment with capecitabine. It was then the patient was found to have DPD deficiency, however, the discovery was too late and failed to prevent her death. Word of caution: do not be lulled into assuming there is no risk with this treatment. Always be vigilant!
10 August 2019 -- Another Victim, Another Advocate for Change
Please see Lynn's Story -- another case of precautionary treatment using 5-FU without thought to a precautionary measure of testing Lynn for DPD deficiency. Her single treatment led to her suffering and death in the UK earlier this year.
Lynn's husband, Chris, is petitioning Members of Parliament and the National Institute of Health to adopt the type of mandatory pre-screening now required in France. More power to Chris and to others who are advocating for this type of change.
28 July 2019 -- Chris Beat Cancer
Earlier this month I received a message from Chris Wark that indicated I might see a spike in people reading pages on this site because he publicized the risk of 5-FU on his site: www.chrisbeatcancer.com
Spike indeed! Thanks Chris for your post entitled "One Dose of 5-FU Chemotherapy Can Kill You". I sincerely hope you helped inspire people to seek testing prior to the start of treatment.
Here's Chris' post: https://www.chrisbeatcancer.com/one-dose-of-5-fu-chemo-can-kill-you/
13 June 2019 -- Another Personal Story Plus Links to Evidence Supporting the Need to Test
Please take a few moments to honor my friend Jane by reading her personal story. Jane and her husband reached out to me before she started her second course of treatment; then I later had the privilege of meeting her during a conference where we each shared our personal experiences with adverse reactions to treatment with 5-FU. Jane passed away in January 2018.
Each year the American Society of Clinical Oncologists (ASCO) hosts a conference that offers the opportunity for professional presentations on the latest developments. This year the topic of 5-FU and pre-screening got a foot in the door. "Screening Patients for Fluoropyrimidine-Related Toxicity Risk" was included in a "poster session". You may find the abstract at:
In addition, Dr Gabriel Brooks and others at the Dartmouth Hitchcock Medical Center had the "Risk of Treatment-Related Death in Carriers of Pathogenic DPYD Polymorphisms Treated with Fluoropyrimidine Chemotherapy: A Systematic Review and Patient -Level Analysis" included in the Meeting Abstracts -- see https://abstracts.asco.org/239/AbstView_239_268243.html
Lastly, a friend shared this citation published this month: "Clinical Implementation of Pre-Treatment DPYD Genotyping in Capecatibine-Treated Metastatic Breast Cancer Patients" -- see https://link.springer.com/article/10.1007/s10549-019-05144-9
We need to continue to see journal articles and professional presentations to advance the need to test patients before the start of treatment. Please share with family and friends who may be preparing for chemotherapy that will include 5-FU so they may ask their oncologists to perform the pre-screening. It is the patients who must demand repeatedly until such screening becomes the standard of care.
8 May 2019 -- Jerri's Story
Today you can now read about Jerri's death caused by a toxic reaction to treatment with 5-FU. Her daughter Terri has been a strong advocate for changing the standard of care and she and her family have a FaceBook site entitled 5futoxicity.
7 May 2019 -- Another Tragic Story Plus News of a Proposed Bill to Require Pre-Screening in New York
Thanks to Joanne for sharing the tragic story of her beloved husband's suffering and for her determined advocacy for change. See her story about David now included in Personal Stories.
Thanks for the effort of Judi Stoddard, who lost her daughter Cheri, the legislature in the state of New York is considering a bill that would require pre-screening. You may find the bill at:
18 April 2019 — “Don’t let perfect be the enemy of good”
That quote attributed to Voltaire came to mind as I re-read recent journal articles concerning pre-screening. True enough there are diverse opinions on the right type of test to perform (I favor phenotyping) but what seems evident is that geno- and phenotype tests help to identify at-risk patients. Some tests serve to also identify enhanced metabolizers that may be receive inadequate dosing.
If we truly intend to personalize the treatment of patients, it seems prudent to pre-determine a patient’s ability to withstand treatment before its start. Unfortunately those responsible for setting treatment standards are 1) dismissing the risk as insignificant, and 2) waiting for the “perfect” test method. And with the second condition the NCCN and FDA are allowing perfect be the enemy of good.
12 April 2019 — product Safety in the News
Today Fisher Price announced a product recall of it’s Rock N Play infant sleeper. Earlier the American Academy of Pediatrics had called for this type of action. There have been 32 infant deaths associated with this product’s use.
While that is tragic, what will it take for the NCCN , ASCO, or the FDA to take action to pre-screen patients when over 1,000 patients die annually?
20 March 2019 -- Recent Finds: Two Helpful Videos and One Disappointing Article
Here is another useful video from OncLive that more clearly addresses the issue of DPD deficiency and the use of 5-FU and capecitabine:
I also came across this video on MedScape where Dr. David Kerr of Oxford is coming out in support of pre-screening. You may need to register as a guest to view this video.
Now of the disappointing article:
While France has advanced to recommend pre-screening prior to the start of this chemotherapy, the US lags behind as it allows the pursuit of “perfection to be the enemy of good” -- waiting for the perfect test when tests today can help reduce the risk to patients. The attached article shows that there remains a big uphill climb to adopt changes that can improve patient outcomes. This article fails to draw attention to the fact that more than 1,000 people will die this year and many more with suffer severe toxic reactions that will require hospitalization after treatment with this commonly used chemo agent: fluorouracil.
4 March 2019 -- OncLive Video Chemotherapy of GastroIntestinal Cancer
I learned recently of another patient who needlessly suffered and died as a result of capecitabine treatment. The wife of the gentleman who passed away is preparing a narrative to share. In the meantime, she shared with me a video made available on OncLive. In this short clip a physician from Cedar Sinai Medical Center of Los Angeles discusses the oncologist's use of chemotherapy and some of the possible side effects. You may view at:
Unfortunately, the presenter fails to discuss just how frequently people suffer severe toxic reactions or the number of fatalities and he also fails to identify that pre-screening may serve to reduce the number of patients exposed to the risk of very adverse treatment outcomes.
Let's hope the next edition of OncLive serves to instruct physicians and patients of the value of pre-screening and dose management to reduce the risk of bad outcomes for patients.
8 Jan 2019 -- Two Pieces of Good News
First, a friend recently shared with me an article she co-authored for a the Clinical Journal of Nursing Oncology. The article is entitled: "5-Fluorouracil and Capecitabine: Assessment and Treatment of Uncommon Early-Onset Severe Toxicities Associated With Administration."
In this article, the authors point out the risk patients face with this course of treatment and offer the Vistogard antidote as a means to help patients recover. It is extremely important to detect adverse symptoms immediately because the antidote is effective only if administered within 96 hours of the last treatment of 5-FU. What I think is very helpful is a "early-onset severe toxicity decision algorithm" which includes a set of recommended actions for the severe symptoms.
Thank you Joanna for your great dedication to improving outcomes for patients treated with 5-FU!
Second, another friend, Dr. Joseph Ciccolini, has reported a breakthrough with French authorities who now call for testing for DPD deficiency before the start of treatment with 5-FU. The
Cancer Institute (INCa) and the Haute Autorité de Santé (HAS) in France has concluded that "
concentration (of uracil) in the blood is today the most reliable technique to determine if the patient has a complete DPD enzyme deficiency.
This review also identifies partial deficits in DPD." And with the acknowledgement that up to 1 in 5 patients treated with 5-FU experience severe toxicities, these organizations recommend
testing of all patients before the use of 5-FU.
Thank you Dr. Ciccolini for your tireless work on behalf of patients! Well done.
Now if only we can get authorities in the US to recognize the risk and to take action as is now happening in France.
13 March 2018
A mother who lost her daughter due to the use of 5FU chemotherapy has been lobbying for change in the state of New York (USA). She has succeeded in get a bill introduced in the New York Assembly. The bill (#SS7710)l proposes to pre-screen patients for DPD deficiency before the start of treatment with 5FU. May hat is off to her for her persistence and determination: 3 1/2 years of effort to get this far.
7 March 2018
I see now that too much time has lapsed since I last posted. So let me just summarize some of what I've learned since I last shared an update. First, I am grateful to Joanna Thompson for making it possible to share the story of Kath and other patients with people who promoted the use of Vistogard, the antidote for 5-FU, and with leaders of cancer patient advocacy groups.
I have since learned that the sales projection for Vistogard is $50 million per year. Part of the sales demand would be for patients whose pump malfunctioned, the remainder for DPD deficient patients (unfortunately I do not know the share of each expected in the sales projection; nonetheless, I think this suggests DPD deficiency is not such a "rare" matter).
The NCCN rejected the petition I submitted in 2017. I plan to submit yet another petition in 2018 and this time I expect to get the help of an oncologist who knows first hand the suffering patients endure when they have the DPD deficiency.
I do have encouraging news to share in the next update but today I conclude with a sad note. I recently learned of the death of Jane Harwood. Two years ago, Jane and her husband reached out to me after she learned her cancer returned. Earlier she discontinued 5FU treatments because of the debilitating effects it had on her. After connecting her with Dr Ciccolini in France, she learned from his findings of her blood work that she could start on a reduced regimen of 5FU. She tolerated the reduced dosage but ultimately with the time lost after stopping her initial treatments, the disease advanced too far.
I had the good fortune to meet Jane in October 2016; we attended the same conference
hosted by the marketers of Vistogard. There, she shared her heart rending story with everyone and proved to be a passionate and articulate advocate for improving the quality of care and for encouraging personalized treatment for patients with DPD deficiency. My condolences to Jane's family; she will be missed.
26 September 2016
See my response to the FDA's partial approval of my petition to revise the drug warning labels.
Next month, I will have the opportunity to meet with another family member who lost a loved one, a survivor of 5FU toxicity, and an oncologist at an event where we will have the opportunity to share our personal experiences in the hopes we raise awareness of the risk to patients. Watch for more to follow.
17 September 2016
I responded to the FDA's assessment of the petitions to change the drug warning labels for fluorouracil and Xeloda. I noted that it is interesting that while the FDA acknowledged factors other than genetics may compromise DPD activity, the revised drug warning still refers to DPD deficiency as solely a genetic condition. I also pointed out that the FDA took a necessary but insufficient step in updating the warning label. Yes it was necessary to indicate severe toxic reactions are not "rare" and I am grateful that the FDA updated the drug label accordingly. By making this change, it will bring attention to the consequences DPD deficient patients suffer when treated, however the FDA chose not to take steps to identify the probability of patients who may be at risk. I believe we must still find a way to promote pre-screening and dose management as ways to minimize the risk of severe toxicities among patients.
On another note, last Saturday, a cancer center in Idaho hosted a workshop for oncologists. A geneticist and research pharmacist led a session on Pharmacogenomics during which they discussed how genetic pre-screening can reduce the risk to patients who are treated with fluorouracil based drugs. I am grateful that more people are becoming aware of the need to use more care before administering this form of chemotherapy for the more people become aware, the sooner we will see changes in treatment practices.
20 August 2016
Good news! The FDA has responded to the petitions to change the drug warning labels for fluorouracil and Xeloda. The Director for the Center for Drug Evaluation and Research agreed to revise the warning labels to more clearly indicate the risk of severe toxicity and the chance of death. The FDA denied the request to require or recommend prescreening or dose management.
The complete response is available at:
Today you will find a new personal story. This time an account of Kathy's journal through treatment and her tale of survival. See Personal Stories -- Kathy's.
12 May 2016
Received word today that the FDA: "We continue to actively work on the response to your citizen petitions." The FDA did approve Vistogard to serve as an "antidote" to an overdose or a rapidly developing severely toxic reaction to 5FU chemotherapy. One might ask if it is necessary to have an "antidote" would it not also make sense to first evaluate a patient's ability to withstand the treatment ("an ounce of prevention....").
22 November 2015
I recently learned of two more deaths: a male patient in CO and a female in TX. Horrible suffering that could and should have been avoided if doctors pre-screened patients. A daughter of the woman in TX has suggested a page on Facebook to help raise awareness -- good idea, watch for that in the near future.
Dr. Ciccolini and colleagues published a study in the British Journal of Clinical Pharmacology that concludes "This feasibility study shows how simplified DPD-based adaptive dosing of 5-FU can reduce sharply the incidence of treatment-related severe toxicities while maintaining efficacy as part of routine clinical practice in digestive oncology." The simplified test method does not look for genetic markers; instead it measures each patient's ability to effectively metabolize the 5-FU. You may read the abstract of this article at PubMed: http://www.ncbi.nlm.nih.gov/pubmed/26392323
Meanwhile in the US, despite the success of tests used in France, the NCCN unanimously rejected my proposal for a pre-screening requirement before the start of chemotherapy. The Colon Cancer Panel concluded: "Based upon review of the data in the references noted in the submission, the panel consensus was to not change the testing language as requested."
8 September 2015
Today La Presse, a newspaper in Montreal Canada, published an article concerning the lack of pre-screening of patients in Quebec prior to treatment with 5-FU (see COMBIEN DE MORTS ÇA VA PRENDRE ?). Marie-Claude Malboeuf, the reporter, notes that pre-screening is used much more frequently in France with growing use in Germany and the UK. She started the article with a story of a male patient who passed away shortly after starting treatment and continues to effectively use personal stories to build a connection with readers, especially those who might be able to bring about change. Thanks to Ms. Malboeuf for promoting awareness of the risk patients face.
27 August 2015
A daughter shared the story of her mother, Linda K. Andersen, and asked that I share it on this web site so I have added another Personal Story. Linda passed away after a single chemotherapy treatment that included 5-FU. Linda's family had her tested for the DPD deficiency, post-mortem, but found no genetic deficiency. The type of "functional", not genetic, test performed by Dr. Ciccolini (see Hope) may been useful in helping Linda avoid the toxic reaction and suffering stemming from her treatment.
6 July 2015
I have heard nothing from the Post so I believe it is safe to say it declined to publish my letter to the editor.
9 June 2015
I submitted a letter to the editor of the Washington Post. The Post prefers letters of 200 words or fewer. Below is my submission (a few words over the quota):
Letter to the Editor of the Washington Post
"Thank you for publishing Medical Mysteries: Toxic chemotherapy. After the loss of my wife, Kathryn, I have come to discover that severe toxic reactions to 5-FU chemotherapy occur all too frequently (estimated at 30% in a 2010 White Paper for Blue Cross/Blue Shield). Severe toxic reactions lead to hospitalizations and even deaths. A “rare” genetic condition (2-8% of the population as reported in your article) fails to explain this phenomenon.
Care providers should and can change the course of treatment by routinely pre-screening patients for DPD deficiency before treatment with 5-FU (or oral capecitabine) then adjust dosage as necessary. This practice has proven successful in Marseilles France where Dr. Joseph Ciccolini routinely screens patients before the start of 5-FU and continues after each treatment; his efforts are showing a sharp reduction in 5-FU related severe toxicities while maintaining treatment efficacy. His test is not genetic: instead it focuses on the functional effectiveness of the DPD enzyme and the patient’s ability to metabolize 5-FU. Sadly, no such test is offered today in the US.
To learn more, see www.know_the_risk_of_5FU_chemotherapy.com where you will find more facts, personal stories, resources, and petitions for change to the National Comprehensive Cancer Network (denied, 2014) and the Federal Drug Administration (pending review since April 2014). "
30 May 2015
I had the honor today to meet with Dr. J. Ciccolini who has published in medical journals his success in testing a patient's DPD activity using a "functional" (aka non-genetic) test. Met him during his visit to the American Society of Clinical Oncology in Chicago. We also met with Dr. S. Chandana from West Michigan who is interested in using Dr. Ciccolini's test capability as a service that will allow him to perform comparative analysis with another test procedure he hopes to institute locally. I hope this meeting leads to a great collaboration between the two.
I was also honored when the patient whose experience was chronicled in the Washington Post called to talk today. She is very interested in combining our efforts to raise awareness concerning DPD deficiency and the threat it poses for those preparing for chemotherapy. I believe this too will become an effective collaboration.
27 May 2015
A friend shared an article from the Washington Post highlighting a personal story of a woman who suffered a severe toxic reaction from this chemotherapy regimen. She survived.
WMUK replayed the interview this weekend; the station replays notable interviews on a holiday weekend. Appropriately done on the Memorial Day weekend.
16 May 2015
Three highlights this week:
1. Followed up with the FDA concerning my petitions to change the drug warning labels. Learned the petitions are still under review; I received no description of the review process or timetable for completion of the review process. I have asked for that information.
2. Spoke with the chief medical officer of a health insurance company and provided additional information for him to share with other professionals who are trying to improve cancer care. Is interested in increasing the collection of data for we agreed the incidence of toxicity associated with fluoropyrimidine drug use is under-reported.
3. Kathryn's oncologist sponsored an oncology resident's abstract that deals with toxic reactions to 5-FU chemotherapy. The resident has been invited to present the paper to other residents on 19 May 2015.
6 Apr 2015
Today I filed a new petition to the Colon/Rectal/Anal panel of the National Comprehensive Cancer Network (NCCN) which will consider petitions in June of this year. See Petitions for Change (to NCCN - "New" 2015) for the submission.
26 Mar 2015
Today Gordon Evans of WMUK, our local National Public Radio affiliate, aired an interview on the subject of DPD
Deficiency and the Risk of 5FU Chemotherapy. Thank you Gordon!
A long way to go to further raise awareness and change practices. As I said during the interview, we need to
focus less on the genetic incidence and more on the rate of toxic reactions which is much greater than predicted by the genetic condition. Only when we start to ask why that is the case will we
begin to take meaningful steps toward improved outcomes for patients.
Thank you all for your continued support.