Joellen Zembruski-Ruple, while she was in the care of the famous MEMORIAL CANCER Center Sloan Kettering of New York City, the first three chemotherapy pills swallowed to treat her carcinoma of squamous cells on January 29, members of her relatives said. They did not realize that the drug could kill her.
Six days later, Zembruski-Ruple went to the Urgent Care Department of Sloan Kettering to treat sores in his mouth and swell around his eyes. The hospital diagnosed oral yeast infection and sent him home, said his sister and his partner. Two days later, they said, he returned in agony, with diarrhea and severe vomiting, and was admitted. “Enzymatic deficiency”, Zembruski-Ruple sent a text message to a friend.
The 65 -year -old man, a patient defender who had worked for the National Multiple Sclerosis Society and other groups, would never go home.
Cover of bruises and unable to swallow or speak, he finally entered hospice care and died on March 25 for the drug that he was supposed to extend his life, said his lifelong partner, Richard Khavkine. Zembruski-Ruple was poor in the enzyme that metabolizes capecitabine, the chemotherapy drug he took, Khavkine and Susan Zembruski said, one of their sisters. Zembruski-Ruple was among about 1,300 Americans every year that die from the toxic effects of that pill or its cousin, the Fluoroucil IV drug known as 5-FU.
Doctors can evaluate deficiency, and then change medications or reduce the dose if patients have a genetic variant that entails risks. The FDA approved an antidote in 2015, but is expensive and must be administered within four days after the first chemotherapy treatment.
The newer cancer medications sometimes include a complementary diagnosis to determine if a medicine works with the genetics of an individual patient. But 5-FU was released in 1962 and sells for approximately $ 17 per dose; The producers of their generic do not seek the approval of the toxicity tests, which generally cost hundreds of dollars.
Doctors have only gradually understood what genetic variants are dangerous in which patients and how to deal with them, said Alan Venook, a specialist in colorectal cancer and liver at the University of California-San Francisco.
When Zembruski-Ruple doctors told him that he had the deficiency, he had been drugged for eight days, said Khavkine, who watched his partner with his sister during the seven-week test.
Khavkine said “I would have asked for the test” if I had known, but added that “nobody told us about the possibility of this deficiency.” Zembruski-Ruple’s sister also said that she was not warned about the fatal risks of chemotherapy or that was counted on the test.
“They never said why they didn’t try it,” Zembruski said. “If the test existed, they should have said that there is a test. If they said: ‘Insurance will not cover it,’ I would have said, ‘here is my credit card.’ We should have known it.”
Orientation moves at a glacial rhythm
Despite the growing awareness of the deficiency, and a defense group composed of friends and afflicted family that presses for the routine tests of all patients before taking the medication, the medical establishment has moved slowly.
A panel of the National Network of Integral Cancer, or NCCN, Sloan Kettering specialists and other main research centers, until recently did not recommend the tests, and the FDA does not require it.
In response to a KFF Health News consultation about his policy, Sloan Kettering Courtney Nowak spokesman said the hospital treats patients “according to NCCN guidelines.” She said the hospital would not discuss the care of a patient.
On January 24, the FDA issued a warning about the enzymatic deficiency in which it urged medical care providers to “inform patients before treatment” about the risks of taking 5-FU and capecitabin.
On March 31, six days after the death of Zembruski-Ruple, the network expert panel for most gastrointestinal cancers took a first step to recommend the tests for deficiency.
Concerned that President Donald Trump’s FDA couldn’t do anything, said Venook, the panel, whose guide shapes oncologists and health insurers, recommended that doctors consider the tests before the dosage of patients with 5-FU or capecitabine.
However, his guide declared that “no specific evidence is recommended at this time”, citing the lack of data to “inform the dose settings.”
Sloan Kettering “will consider this guide in the development of personalized treatment plans for each patient,” Nowak told Kff Health News.
The new NCCN guide “was not the general recommendation we were working on, but it is an important step towards our final objective,” said Kerin Milesky, a public health official in Brewster, Massachusetts, which is part of a defense group for the tests. Her husband, Larry, died two years ago at 73 years after a single capecitabine treatment.
European medication regulators began to urge oncologists to evaluate patients in search of deficiency in May 2020. Patients with potentially risky genetics begin with a half dose of the drug against cancer. If they do not suffer important toxicity, the dose increases.
An ultimatum that saves lives?
Emily Alimonti, a 42 -year -old biotechnology seller in the state of New York, chose that path before starting capecitabin treatment in December. She said her doctors, including an oncologist from Sloan Kettering, told her that they didn’t do deficiency tests, but Alimonti insisted. “No,” he said. “I am not starting until I recover the test.”
The test showed that Alimonti had a copy of a variant of risky genes, so doctors gave him a lower dose of the medication. That has even been difficult to tolerate; She has had to omit dose due to low white blood cell counts, Alimonti said. She still doesn’t know if her insurer will cover the test.
Around 300,000 people are treated with 5-FU or capecitabine in the United States every year, but their toxicity could well have avoided the approval of the FDA if it had approved the approval today. However, in the absence of withdrawing a medication, US regulators have little power to handle their use. And 5-FU and Capecitabine are still powerful tools against many types of cancer.
In a January workshop that included FDA officials and cancer specialists, Venook, the co -chair of the NCCN panel, asked if it was reasonable to recommend that doctors obtain a genetic test “without saying what to do with the result.”
But Richard Pazdur, the main expert in FDA cancer, said it was time to put an end to the debate and start the tests, even if the results could be ambiguous. “If you don’t have the information, how do you have advice?” asked.
Two months later, the Venook panel changed course. The price of the tests has fallen below $ 300 and the results can be returned as soon as three days, said Venook. The doubts about the FDA’s ability to face the problem stimulated the change of panel’s opinion, he said.
“I don’t know if the FDA will exist tomorrow,” Venook told Kff Health News. “They are carrying a demolition ball to common sense, and that is one of the reasons why we felt we had to move forward.”
On May 20, the FDA published a notice of the Federal Registry in search of public information on the subject, a measure that suggested that it was considering new measures.
Venook said that he often proves his own patients, but the results can be confused. If the test finds two copies of certain dangerous genetic variants in a patient, avoid using the medication. But such cases are rare, and Zembruski-Ruple was one of them, According to his sister and Khavkine.
Many more patients have a single copy of a suspicious gene, an ambiguous result that requires a clinical judgment to evaluate, said Venook.
A complete scan would provide more information, but add expenses and time, and even then the answer can be cloudy, said Venook. He worries that starting patients with lower doses may mean less priests, especially for newly diagnosed colon cancer patients.
Power must rest with patients
Scott Kapoor, a doctor of the Emergency Room in the area of the Toronto area, whose brother Anil, a very dear urologist and surgeon, died of 5-FU toxicity at 58 years in 2023, considers that Venook’s arguments as medical paternalism. Patients should decide whether to evaluate and what to do with the results, he said.
“What is better: don’t tell the patient about the test, don’t try them, potentially the mates in 20 days?” said. “Or tell them about the tests while warning that cancer will kill them in a year?”
“People say that oncologists do not know what to do with the information,” said Karen Merritt, whose mother died after an infusion of 5-FU in 2014. “Well, I am not a doctor, but I can understand the report of the Mayo Clinic about it.”
The Mayo Clinic recommends starting patients with half a dose if they have a suspicious variant. And “the vast majority of patients can begin treatment without delays,” said Daniel Hertz, a clinical pharmacologist at the University of Michigan, at the January meeting.
Some hospitals began to try after patients died due to deficiency, said Lindsay Murray, from Andover, Massachusetts, who has advocated generalized tests since his mother was treated with capecitabin and died in 2021.
In some cases, said Venook, relatives of dead patients have sued hospitals, leading to settlements.
Kapoor said his brother, like many patients of non -European origin, had a variant of genes that has not been widely studied and is not included in most tests. But a complete scan would have detected it, said Kapoor, and such scanning can also be done for a few hundred dollars.
The change of changed language of the cancer network panel is disappointing, he said, although “better than anything.”
In video tributes to Zembruski-Ruple, her friends, colleagues and customers remembered her as kind, useful and attractive. “Joellen was beautiful both inside and outside,” said Barbara McKeon, former colleague of society ms. “She was fun, creative, she had a great sense of style.”
“Joelllen had this balance of bad and playful bad behavior,” said the Psychotherapist Anastatia Fabris. “My beautiful, vibrant, fun and loving friend Joellen.”
