Overdosing on chemotherapy

Each year, over 275,000 cancer patients in the United States receive an infusion of a drug called fluorouracil (5-FU), or take a similar oral medication called capecitabine. While these are common chemotherapy treatments, they can be deadly for around one in 1,000 patients.

Patients who are deficient in an enzyme that metabolizes 5-FU and similar drugs will essentially overdose on chemotherapy because they stay in their bodies for hours. Around one in 50 people who receive these drugs become severely ill or hospitalized, and hundreds of people each year die from the drugs.

"Your body burns from the inside out," said Lindsay Murray, whose mother, Carol Rosen, died after receiving chemotherapy for metastatic breast cancer. Rosen experienced severe symptoms after her treatment, including kidney and liver failure.

According to Allen, doctors can easily test patients for a genetic variant that puts them at a higher risk of having this deficiency. If a patient is at risk, doctors can then either switch medications or lower the dosage of a drug.

However, a recent survey found that only 3% of U.S. oncologists regularly order these tests before administering patients with 5-FU or capecitabine. Although FDA has added new warnings about 5-FU's lethal risks, it does not require doctors to test for the enzyme deficiency before administering chemotherapy.

The National Comprehensive Cancer Network (NCCN), which issues the most widely followed U.S. cancer treatment guidelines, also does not recommend preemptive testing for the deficiency. Alan Venook, an oncologist from the University of California, San Francisco and co-chair of NCCN, said he does not believe that testing should be mandatory since the results are often unclear and could lead to undertreatment.

"If one patient is not cured, then you giveth and you taketh away," Venook said. "Maybe you took it away by not giving adequate treatment." He also added that "unhelpful information may lead us in the wrong direction."

Advocates push for more gene testing before chemotherapy

Since 2020, British and European Union drug authorities have recommended cancer patients be tested before receiving chemotherapy. Now, a growing number of health advocates, professional groups, and U.S. hospital systems — including the American Cancer Society — are following suit and endorsing routine testing for cancer patients. In general, most public and private insurers will cover the costs of the tests.

Dana-Farber Cancer Institute began testing for genetic variants of deficiencies after Murray wrote to its chief quality officer, Joe Jacobson, about her mother's death. The hospital now has a testing system that covers over 90% of patients with a potential deficiency, and in its first 10 months of use, around 50 patients with risky variants were detected.

Some advocates are also pushing for broader genetic tests to be used since most only check for four variants, which may not always apply to patients of certain ancestries. For example, different variants are responsible for deficiencies in people of African ancestry compared to those of European ancestry.

There is an eight-variant and 11-variant version of the test available. There are also tests that can scan for hundreds of variants that could potentially slow the metabolism of chemotherapy drugs, but they take longer to administer and are more expensive.

Scott Kapoor, an ED physician from Toronto whose brother died of 5-FU poisoning, said patients should be aware of the potential risks before they receive chemotherapy.

"You tell them, 'I am going to give you a drug with a 1 in 1,000 chance of killing you. You can take this test. Most patients would be, 'I want to get that test and I'll pay for it,' or they'd just say, 'Cut the dose in half,'" Kapoor said.

According to Murray, she believes more hospitals will begin to have mandatory testing, especially if there are more lawsuits over the matter. In 2022, Oregon Health & Science University paid $1 million to settle a lawsuit after a chemotherapy overdose death.

"What's going to break that barrier is the lawsuits, and the big institutions like Dana-Farber who are implementing programs and seeing them succeed," Murray said. "I think providers are going to feel kind of bullied into a corner. They're going to continue to hear from families and they are going to have to do something about it." (Allen, KFF Health News, 3/26)

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