Experts have sounded the alarm about hundreds of cancer patients dying preventable deaths due to a lethal side effect of chemotherapy treatment.
The complication, which affects one in 50 patients, destroys healthy cells in the body, eventually leading to multiple organ failure and, in the worst cases, death.
It effects those given some of the most common types of chemotherapy who lack specific enzymes required to metabolize the drug.
Experts say there are tests to determine the unlucky patients who will suffer the adverse effect – but not enough doctors are using them.
Dr Steven Offer, a cancer researcher and associate professor of pathology at the University of Iowa Carver College of Medicine, told CBC News: ‘One thing that strikes home is these patients are dying because of their treatment … and not necessarily dying because the cancer has progressed.’
Carol Rosen, 70, died after taking a routine dose of the chemotherapy pill capecitabine
They have also urged public health authorities to provide clear warning labels on medications.
Dr Daniel Hertz, a pharmacist and associate professor at the University of Michigan College of Pharmacy, told KFF Health News: ‘FDA has responsibility to assure that drugs are used safely and effectively.’
Failing to do so, he said, ‘is an abdication of their responsibility.’
One patient to suffer the devastating complication is Carol Rosen, a 70-year-old retired teacher in Massachusetts, who began taking chemotherapy pills for metastatic breast cancer in January 2021.
In the weeks to come, she suffered severe diarrhea, nausea, and mouth sores that kept her from eating, drinking, and speaking.
The skin peeled off her body, and her kidneys and liver shut down.
‘Your body burns from the inside out,’ Ms Rosen’s daughter, Lindsay Murray, told KFF News.
Ms Rosen had an on capecitabine – the pill form of chemotherapy known to cause the problem, taken by more than 275,000 cancer patients across the US.
Instead of killing her cancer, capecitabine attacked surrounding organs until she eventually died, making her one out of hundreds of patients a year to lose her life to what is supposed to be lifesaving chemotherapy.
Another type of chemotherapy known to elicit similarly serious complications in those lacking specific enzymes is fluorouracil (also commonly known as 5FU).
A report published by BMJ Oncology estimates that a record two million Americans will be diagnosed with cancer this year. About half of those will receive chemotherapy or radiation, according to the CDC.
Chemotherapy is a drug treatment meant to kill fast-growing cells like cancer cells.
There are several different drug options in chemotherapy, and the specific one a patient is prescribed depends on their form of cancer, how aggressive it is, and other factors like pre-existing conditions.
However, while the drug is meant to kill malignant cells, its main risk is that it can also destroy healthy cells around them like blood cells and hair follicles.
According to the American Cancer Society (ACS), this can lead to side effects like fatigue, hair loss, easy bruising, anemia, nausea, vomiting, appetite changes, weight changes, skin and nail changes, difficulty concentrating, bladder issues, mood changes, and fertility problems.
But these complications can be especially deadly if a patient has an extremely toxic reaction to certain chemotherapy medications, or is given the drugs in unreasonably high doses.
This can lead to dangerous symptoms like extremely slow heart rate, heart attack, convulsions, pain during urination, slow breathing, severe pain, nausea, vomiting, diarrhea, high fever, heavy bleeding, and coma.
In the UK, it is now recommended that doctors test for the genetic predisposition to chemotherapy complications, after cases like that of Keith Gadd (pictured) came to light. The 73-year-old farmer had started taking capecitabine in 2018 and after five days using the drug his health deteriorated
‘Chemotherapy is designed to kill cells under the premise that cancer cells are dividing and growing faster, and are more susceptible to the chemotherapy than are healthy cells,’ Dr Hertz told DailyMail.com.
‘If a patient is overdosed, there will be too much chemotherapy in their body for too long, which will lead to the death of non-cancerous cells and clinically overt toxicity as individual organs die.’
Recent research estimates that chemo complications kill about 1 in 1,000 patients, which amounts to hundreds a year.
And as many as one in 50 chemo patients become severely ill or hospitalized.
It is thought that the majority of people with lethal reactions suffer a genetic problem that leads to a deficiency in certain enzymes in the liver that can metabolize chemotherapy.
Researchers have focused on deficiency in one enzyme, called dihydropyrimidine dehydrogenase – or DPD – which is thought to impact up to eight percent of the population.
Some scientists refer to this deadly complication as a chemotherapy ‘overdose’, as the deficiency causes the medications to stay in the body longer before being excreted.
‘In terms of the fluoropyrimidines (e.g., 5-fluoruracil and capecitabine), giving a standard dose to a patient with DPD deficiency would constitute an overdose and typically causes severe toxicity, and in some unfortunate instances causes death,’ Dr Hertz said.
‘DPD deficiency is the most common cause of overdose from fluoropyrimidine chemotherapy.’
Testing blood draws and cheek swabs can check for DPD deficiency and genetic risk factors, and results usually come back within a week. This allows doctors to quickly switch drugs or lower the dosage.
However, a 2022 survey in the journal JCO Oncology Practice found that just three percent of oncologists routinely order this testing before giving patients the medicine.
This could be because the National Comprehensive Cancer Network, which issues US cancer treatment guidelines, does not recommend preemptive testing.
The FDA added warnings about the potentially lethal risks of 5-FU to the drug’s label on March 21, though it does not require doctors to perform testing.
Drug authorities in the UK and elsewhere in Europe, however, began recommending the tests in 2020.
Another patient to suffer the wrath of DPD deficiency is Dr Anil Kapoor, a urologist from Canada.
In January 2023, Dr Kapoor was treated with his first intravenous dose of fluorouracil (5-FU), a chemotherapy nearly identical to capecitabine, before succumbing to overdose.
Dr Amil Kapoor, a 58-year-old urologist from Canada, died three weeks after taking a single dose of chemotherapy for stage four colon cancer
The 58-year-old had been diagnosed with stage four colon cancer just three weeks earlier, and tests conducted after his death showed that he had a genetic variant that made 5-FU toxic to him.
‘He started vomiting and feeling extremely nauseated. And within 24 hours, he had inflammation in the mouth and throat,’ his brother, emergency room physician Dr Scott Kapoor, told Go Public.
‘He could not eat or drink anything and he was also having profound diarrhea.’
Dr Kapoor’s son, Akshay, told Go Public: ‘It was honestly a cruel rollercoaster of emotions. I feel like we were robbed of our time together.’
Seven months after his brother’s death, Scott told KFF Health News that he met a woman who had lost her husband after he took a single dose of 5-FU at age 77.
The man was Judge Gary Markwell of Ball Ground, Georgia, who died in September 2022. His obituary states that his death was from a ‘severe reaction to oral chemotherapy.’
In 2015, the FDA approved uridine triacetate, the first drug to reverse 5-FU or capecitabine overdoses in adults and children.
The drug is administered orally and is meant to block cell damage from chemo.
Though it can be taken up to four days after chemo is administered, the manufacturers recommended using it as soon as an overdose is suspected.
