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

Kathryn's Case

A Journal of the Kathryn Case

The following is the story of Kathryn, an improbable case of a rectal cancer patient.  Kathryn got into treatment right after receiving her diagnosis. The medical statistics, the probabilities, indicated she should suffer little when undergoing the FOLFOX chemotherapy regimen.  Three different cancer centers assured her that this chemotherapy regimen is “fairly well tolerated”. 

Not so, in Kathryn’s case.  It turned out she lacked the enzyme, dihydropyrimidine dehydrogenase,  necessary to metabolize the 5-FU chemical agent .  This is a genetic condition called the dihydropyrimidine dehydrogenase deficiency (DPD).   As a result of this condition, the 5-FU chemo agent remained in her body continuing to destroy healthy cells than for a much longer period of time than found in patients without the DPD condition. 

This led to complications from muscositis and neutropenia from which Kathryn never recovered, the consequence was  fatal.  

Her story is given here so we may learn from her case and minimize the probability of others suffering the same fate.

Living a Healthy Life Until…

Kathryn did not seek medical treatment for many years because she took care of her mind and body.  She walked five days a week for a total of 15 miles.  Kathryn took great care not to introduce unnecessary chemicals into her system.  When she would have a setback, rarely would she take anything for relief but when she did, it was a very small dosage of ibuprofen.  

Changes in her body forced her to seek medical advice in 2012.  What she thought was a bad hemorrhoid (years back she was told she had one) became increasingly uncomfortable; so uncomfortable she finally scheduled an appointment with a physician.  Soon after scheduling the appointment, she discovered a swelling in her groin, a lymph node, and requested an earlier appointment.  Her care providers moved with alacrity.

Diagnosing the Problem

The physician assistant at her family health practice performed an examination and immediately referred Kathryn to a colorectal surgeon for a colonoscopy.

The surgeon performed the colonoscopy and removed tissue of the tumor he discovered for a biopsy.  That was a Friday. On Monday Kathryn learned the biopsy results indicated she indeed had cancer.

Seeking a Treatment Plan

Between the time of diagnosis and the beginning of treatment, Kathryn, her son, and husband met with three different medical practices each of whom had respected track records.

Kathryn and her family sought advice from three different cancer centers.  The oncologists were uncertain about how the cancer spread to the inguinal lymph node so staging the cancer was a bit uncertain: they varied on whether the cancer was late stage III or early stage IV.  CT scans showed that the cancer had not spread to the lungs or liver which is found in late stage IV.

Each oncologist recommended a similar course of treatment, chemotherapy, radiation in conjunction with chemotherapy, and surgery, though they differed in the recommended sequence.  

Given Kathryn’s advanced stage of rectal cancer, each practice also indicated she should expect surgery (though the extent of the surgery ranged from a colostomy to evisceration).  She was resigned to the colostomy and even joked about having a special bag for nights of romance; she was not, however, comfortable at all about the effects an evisceration would have on her quality of life.

Each set of physicians recommended a form of chemotherapy, FOLFOX, commonly administered for advanced colorectal cancers, and each assured Kathryn that the regimen is “fairly well tolerated” and that she would not lose her hair or suffer debilitating side effects.  The FOLFOX drug combination includes leucovorin calcium (folinic acid), fluoroucil (aka 5-FU), and oxaliplatin.

Starting Treatment (Chemotherapy)

In fewer than three weeks, Kathryn had gone from detection to her first dose of chemotherapy.  She wanted to start right away and then vacation in a rustic cabin the following week – it was where she found peace and could re-center her soul.  The treatment center could not schedule her quickly enough so she and the oncologist agreed to have the first treatment administered in the hospital.

Kathryn entered the hospital on a Wednesday.  She was pleased to learn that she did not suffer an immediate adverse reaction to the chemo as her mother-in-law experienced.  She did experience tingling and a loss of feeling in her hands, neuropathy, after the oxilaplatin treatment and nausea after the 5-FU.  After sixty hours in the hospital, she returned home to rest.  That was Friday night.

Tracking the Effects of the Chemotherapy

Her first day home, a Saturday, Kathryn experienced typical symptoms of nausea, lack of appetite, and low energy level. 

As soon as Sunday, her 2nd day home, Kathryn experienced a very sore tongue which was white in appearance. She followed the instruction guide from the cancer center and called to report the symptom but received no treatment that day – the on call oncologist concluded this was too early for any concern. The condition of her mouth worsened the next day, Monday, as it affected the entire tongue.  Her oncologist prescribed “magic mouthwash” and folic acid to treat the thrush (yeast infection).   Kathryn had little appetite.  She drank a sports drink or two and ate a cup or two of pudding.

By Wednesday, Kathryn had seen no increase in her energy level and she noticed her lips had become numb and swollen – possible side effect of the “magic mouthwash”.  Thursday brought about another change that led to a trip to the cancer clinic.

Kathryn reported the development of red spots on her legs and thorax.  The nurse from the cancer asked her to come in for blood work.  The test results showed her platelet level within an acceptable range. While at the cancer center, as luck would have it, her oncologist spotted her and asked her to come in for an examination – he noticed her clearly weakened state.  Kathryn shared with him that she felt a burning sensation during urination and that she had not been able to consume much in the way of food or liquids.  The doctor ordered a urinalysis (results showed no infection) and a saline IV.  Kathryn was noticeably more energetic after the IV, not her normal level of energy but better.  She was able to go visit her newborn grandson and hold him for the first, and last, time.

The next day, Friday, many friends stopped by to wish her well and to encourage her.  She was noticeably weakened at dinner time and did not engage in conversation as normal.  She also noticed her hair starting to thin.  Later that night, diarrhea struck suddenly and caught her completely by surprise.  She took to wearing underpads after that.

Saturday was a fairly relaxed day for her but again it was a relatively low energy level day and one during which she consumed only one or two sport drinks and pudding.  The skin on her lips and around her genital and rectal areas became increasingly irritated and required the application of a lotion to soothe the discomfort.  Her mouth remained sore and she started to use a waterpik device because brushing became intolerable.  While dozing off to sleep for the night, she sent off a series of body tremors that neither of us caught as a warning sign to suggest that the next day things could turn worse.

Sunday morning Kathryn awoke and used the bathroom which was only several steps away from her bed.  She did not have the strength to return to bed and she had to stop to regain her strength before returning to bed.  Kathryn later emerged from the bedroom and met her husband with an embrace.  She then slowly slipped through the arms of her husband onto the floor with a vacant look in her eyes and a smudge of blood on the side of her mouth.

 Rushing Back to the Hospital

The emergency responders came right away, started an IV of saline, and delivered her promptly to the same hospital where she received the chemotherapy.  Her jaw area and lips were noticeably swollen and she had developed a couple of scabs on her face near her nose.  After receiving care which restored Kathryn’s attentiveness, the on-call oncologist from the cancer center observed her condition and concluded that she suffered from neutropenia and that she lacked an enzyme necessary to metabolize the 5-FU agent.  As a result of the enzyme deficiency, the 5-FU would remain in her system much longer than for most patients and would continue to damage normal cells along with her cancerous cells. The doctor admitted her to the hospital and started her on antibiotics and an IV with nutrients.

During her hospitalization, her family stayed with Kathryn every hour of the day.  They helped her suction the mucous she had difficulty clearing from her mouth.  Her mouth remained swollen and sore Monday so she communicated by writing notes instead of speaking.  Though she needed to tow along her IV tree, she had plenty of strength to get up and move back and forth to the bathroom.

The next day she continued to communicate by writing notes and she was attentive enough to read on her own for periods of time.  New symptoms arose as she experienced pain while urinating – turns out it was not an infection. The pain was attributed to the skin around her genital area and anus has become increasingly irritated – the appearance made the nurses wince.  The next day the wound nurse came to recommend treatment for the skin.  The good news: her lungs were clear. The bad news: no new white blood cells and her platelet count decreased.

Wednesday Kathryn’s breathing weakened and she reported that she felt as though she had to fight against drowning.  She suffered discomfort from intestinal gas which led to frequent trips to the restroom; her output was dark green and not solid. A spot of blood appeared in her urine. At times she showed slight signs of trembling.  No change in her white blood cell level or skin condition.

Her mucous production continued to require frequent suctioning Thursday but that effort was not keeping up with the production and her mouth showed signs of the build up there and signs of skin in her mouth sloughing off.  A chest x-ray showed that her lungs remained clear.

On Friday, Kathryn started to retain fluids. The diuretic prescribed by her doctor naturally caused frequent trips to discharge the fluids. Kathryn started to use the portable commode and did so on her own strength.  The sores on her face started to heal and the red spots subsided but the skin around her elbows became red so she received a new mattress to help prevent bed sores.  Kathryn’s breathing became more labored but improved after a respiration therapist worked long and hard to clear her mouth and air passage way of dead skin and mucous.

Respiration therapy continued on Saturday and succeeded in removing a fair amount of mucous by inserting a catheter through Kathryn’s nostril – she did not want another workout of her mouth.  She suffered a lot of cramping in her bowels.  Her strength declined and she was unable to catch and move herself before she had a bowel movement in her bed.  The on-call doctor said she should expect to take several weeks to recover and that her exhaustion may increase before it lessens.  Still no signs of improvement in her blood system.

On Sunday, the start of week 2 in the hospital, Kathryn started to suffer significant pain associated with her digestive system (7 on a scale with 10 the highest); her accidents in bed became routine and when she did move to the commode, she needed assistance.  The respiratory therapist returned for more work and observed that Kath’s lungs sounded better but could not get her to produce a cough.  Insulin was given to help with her blood sugar.

Her son discovered an FDA “orphan” drug, vistonuridine, that can be used to treat patients who suffer an overdose of 5-FU.  He discussed this with the oncologist and learned that the time window for treatment had passed and that the drug could be administered only for intentional overdoses.

The first signs of vomiting appeared on Monday.  Kathryn’s breathing became more labored as she had “stuck breaths” every 10 minutes.  In the early morning she awoke in pain, became disoriented and tried to disrobe several times.  No progress on the white blood cell production.

Slipping Further

Kathryn spent much of the day vomiting on Tuesday.  The vomiting was frequent, in large volume, and its content was dark green and included mucous.  The nurses spent much of the day cleaning after her because Kathryn was too weak to care for herself.  More importantly though, the vomiting became a danger when she vomited while undergoing respiratory therapy and it appeared she may have aspirated some of the vomit.  

Her doctor ordered a series of CT scans to check her head, chest, and abdomen.

Later in the day, her blood oxygen level dropped and she started to receive oxygen. The attending nurse became concerned with Kathryn’s lack of responsiveness and consulted with the oncologist who advised against admitting her to intensive care at that point.  Kathryn continued to suffer from intestinal pain.

Wednesday the skin around her mouth appeared hard and swollen but she mustered a yawn and laugh.  On the positive side, her skin appeared to improve, the vomiting stopped, and she required less pain medication.  Unfortunately, her blood oxygen level dropped and she started to require oxygen. 

The noticeable turn in Kathryn’s condition led her oncologist and her husband to discuss how they should respond if she suffered respiratory distress.  Her husband agreed to intubation only if for a short period of time and if it served to enable her recovery.  Her oncologist indicated that he still envisioned her walking out of the hospital. 


Thursday morning right after a bed change, her husband noticed Kathryn’s face had started to turn blue so he alerted the nurses who issued a distress call. The intensive care unit (ICU) responded immediately and intubated Kathryn while her husband stood nearby.

Before admitting her to ICU, the attending ICU doctor ordered a series of tests.  The staff discovered that Kathryn’s abdomen was distended and hard so they suctioned out air and mucous.  There were no signs of trouble with her head or kidneys.  The doctor reported that she suffered from a partially collapsed left lung (probably as a result of aspiration on Tuesday).  He also expressed concern with her ability to stay ahead of her mucous production and all of her work to expel the mucous is weakening her.  Kathryn’s mucositis had now become a greater concern than her neutropenia.  The doctor recommended giving her a quiet night of rest.

On Friday Kathryn’s blood pressure dropped a couple of times and her temperature rose to 100.7 until ICU administered a drug to reduce the temperature.  When nurses did a spontaneous dialing back on the respirator, Kathryn offered only a weak response of breathing on her own.  A bronchoscopy removed a mucous plug from her left lung; the procedure discovered signs of inflammation but no infection.  The attending doctor in ICU spent a great deal of time with Kathryn’s family (children, brothers, and husband) to discuss his observations and to answer the family’s many questions.  He indicated that the longer a patient stays on a respirator, their dependency on the device increases.  So he recommended testing Kathryn’s response on Saturday to see if he could “liberate” her from the respirator; the family agreed with the plan.

When the nurses scaled back the respirator’s support, Kathryn showed a positive enough response that the nurses “liberated” her before mid-day Saturday.  Though the nurses stopped the sedation that accompanied the use of the respirator, Kathryn’s response remained weak though at one instance she did move her lips to express “I love you”.   The attending ICU doctor said he planned to try to control her mucous by suppressing its formation and through suctioning.

Kathryn appeared to manage well enough that many of her family had left the hospital in the early evening.  However, at 1745 hours the attending ICU doctor had become concerned with Kathryn's weakened condition and her ability to stay ahead of her mucous production so he summoned her husband to return to the hospital to consult on treatment options.  The doctor knew that, in accordance with her wishes, Kathryn’s family did not want to keep her on the respirator indefinitely.  The doctor also advised against a tracheotomy due to her weakness. Without any other actions, he was concerned about her ability to survive the evening.  Her family reviewed Kathryn’s options, discussed them with the attending doctor, and concluded that they would take no further invasive actions and if Kathryn did not rally to recover, they would ask for palliative care.  Not long afterward, it became clear that these were her final hours and the nurses administered palliative care as Kathryn’s family and friends circled around her in ICU. Kathryn stopped breathing at 2210 hours and her strong heart finally beat its last at 2235 hours.

Learning from this case

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.”  A posting from the blog Kathryn maintained during her short experience as a cancer patient.

What can we learn from Kathryn’s case?  We have learned that not everyone tolerates 5-FU fairly well.  As it turns out 5% or fewer of the patients treated suffer the same enzyme deficiency as Kathryn.  Though that is a small percentage, clearly the consequences of an inability to metabolize 5-FU can become fatal. 

Given that, it seems prudent to introduce risk management practices in the treatment of patients who may be scheduled to receive 5-FU.  This could include:  

  • Screening patients for the requisite enzyme instead of assuming the treatment will be fairly well tolerated.
  • If screening practices are not mature enough to reliably serve as indicators, test the ability of patients to tolerate FOLFOX treatment regimen by administering low doses and incrementally build dosages to full strength.
  • Establishing staging indicators to facilitate the early detection of the inability to metabolize 5FU – analogous to the staging of cancer. Consider the timing and the severity of each symptom along with the coincidence of multiple symptoms as warning signs.
  • Developing an early intervention treatment plan in conjunction with earlier detection efforts to minimize the damage to the digestive, respiratory, and circulatory systems (e.g. the use of vistonuridine, an FDA orphan drug).

Perhaps the sharing of Kathryn’s case can further serve to promote more effective treatment regimens for patients as improbable, as special, as her.


(written Jan 2013)