May 29, 2024

Saving Hundreds of Lives Annually: The Potential of a Routine Gene Test for Chemotherapy Overdosing

Saving Hundreds of Lives Annually: The Potential of a Routine Gene Test for Chemotherapy Overdosing

In the realm of cancer treatment, advancements are constantly being made to enhance effectiveness while minimizing risks. One such breakthrough that is gaining traction is the use of gene testing to tailor chemotherapy doses. This approach isn’t just about refining treatment plans—it’s about saving lives.

The Perils of Overdosing on Chemotherapy

Chemotherapy, while a powerful weapon against cancer, is a double-edged sword. Administering the correct dosage is crucial for its effectiveness. Too little, and the cancer might not respond adequately. Too much, however, it can lead to severe side effects, complications, or even prove fatal. Overdosing on chemotherapy is a real concern, and its consequences can be devastating. This is where the significance of routine gene testing comes into play.

Unveiling the Potential of Gene Testing

Imagine a scenario where, before starting chemotherapy, a simple gene test could reveal how a patient’s body processes drugs. This information would allow doctors to tailor the dosage precisely to each individual’s genetic makeup. This is not just a hypothetical scenario—it’s becoming a reality for many cancer patients. Gene testing has the potential to revolutionize chemotherapy treatments by personalizing them to each patient’s needs.

How Gene Testing Works

Gene testing, also known as pharmacogenomics, analyzes a person’s genetic variations to predict how they will respond to medications. In the context of chemotherapy, this means understanding how a patient’s genes affect their body’s ability to metabolize and eliminate cancer drugs. By identifying genetic markers associated with drug metabolism, doctors can make informed decisions about the appropriate dosage for each patient. This not only improves treatment outcomes but also reduces the risk of adverse reactions.

Saving Lives, One Test at a Time

The impact of routine gene testing for chemotherapy overdosing cannot be overstated. By avoiding unnecessary overdoses, patients can experience fewer side effects, better quality of life during treatment, and, most importantly, improved survival rates. Statistics suggest that hundreds of lives could be saved each year by implementing this simple yet powerful tool. It’s a small step in the world of cancer treatment, but one that holds immense promise for patients and their families.

Embracing a Personalized Approach to Care

As we move forward in the fight against cancer, personalized medicine is emerging as a beacon of hope. Gene testing is a prime example of how we can tailor treatments to individuals, making healthcare not just effective but also safer and more precise.

The potential of routine gene testing for chemotherapy overdosing is clear—it’s a game-changer in the quest to save lives. By embracing this innovative approach, we can pave the way for a future where cancer treatments are not only more effective but also more compassionate.

A Tragic Tale Unveiled

On a chilly morning in January 2021, Carol Rosen underwent a common treatment for metastatic breast cancer. Three harrowing weeks later, she succumbed to the excruciating effects of the very drug intended to extend her life.

Aged 70, retired schoolteacher Rosen spent her final days in torment, grappling with intense diarrhea, unrelenting nausea, and painful mouth sores that prevented her from eating, drinking, and eventually, speaking. Her body suffered, skin peeling away as her kidneys and liver faltered. Lindsay Murray, Rosen’s daughter from Andover, Massachusetts, described the experience: “Your body burns from the inside out.”

Rosen was among the 275,000 cancer patients in the U.S. who receive infusions of fluorouracil (5-FU) or, like Rosen, take the pill form known as capecitabine each year. While chemotherapy is no easy journey for anyone, for patients lacking an enzyme crucial for metabolizing these drugs, the consequences can be agonizing or fatal.

In these cases, patients effectively overdose because the drugs linger in their bodies for extended periods instead of being swiftly metabolized and expelled. It’s estimated that these drugs claim the lives of 1 in every 1,000 patients who take them—amounting to hundreds yearly—and severely afflict or hospitalize 1 in 50. Doctors have the means to test for this deficiency and receive results within a week. They can then adjust treatments, either changing medications or reducing dosages for patients carrying genetic variants that pose risks.

The Battle Over Preemptive Testing

Surprisingly, a mere 3% of U.S. oncologists routinely order these tests before administering 5-FU or capecitabine, largely due to the National Comprehensive Cancer Network’s guidelines, which do not advocate for preemptive testing.

In response to inquiries from KFF Health News about its policies, the FDA added new warnings to 5-FU’s label on March 21. However, it did not mandate the testing before prescribing the chemotherapy.

Explaining their stance, the FDA stated they could not endorse the 5-FU toxicity tests as they had not reviewed them. This decision, according to Daniel Hertz, an associate professor at the University of Michigan College of Pharmacy, contradicts the FDA’s responsibility to ensure safe and effective drug usage.

While the FDA’s update is considered a step forward, Hertz insists it falls short of the needed overhaul. Meanwhile, across the pond, British and European Union drug authorities have recommended testing since 2020. A growing number of U.S. hospital systems, professional bodies, and health advocates, including the American Cancer Society, also champion routine testing. Most insurers in the U.S., public and private, cover these tests, with Medicare reimbursing $175, though costs might vary based on the number of variants screened.

Advocacy for Change and Action

The latest guidelines from the Cancer Network on colon cancer acknowledge that not everyone with a risky gene variant will suffer adverse effects from the drug. Lowering doses for such patients could, however, jeopardize their chances of a cure or remission. Many panel doctors, such as University of Colorado oncologist Wells Messersmith, claim never to have witnessed a 5-FU-related death.

In European hospitals, the practice is to start patients with a reduced 5-FU dose if tests indicate poor drug metabolism. If patients respond well, the dose is gradually increased. Advocates for this approach criticize U.S. oncology leaders for unnecessary delays, arguing that these delays harm patients.

Gabriel Brooks, an oncologist and researcher at the Dartmouth Cancer Center, blames the rigidity of those on oncology panels, stating, “We are oncologists, drugs are our tools, we don’t want to go looking for reasons not to use our tools.” This entrenched attitude, he believes, hinders progress.

Oncologists are familiar with the toxicity of chemotherapy, often adopting a “no pain, no gain” mentality. 5-FU, introduced in the 1950s, has been a staple in cancer treatment.

However, as Robert Diasio from the Mayo Clinic, involved in major studies of the genetic deficiency in 1988, points out, the tide may be turning. He asserts that any healthcare provider who has experienced a patient’s agonizing death due to these drugs would advocate for universal testing.

While genetic tests matching tumors with specialized drugs are common in cancer care, safety-focused gene tests like these are not as widely utilized, notes Mark Fleury, policy director at the American Cancer Society’s Cancer Action Network.

In other medical fields, such as cardiology, similar delays in implementing advancements are observed. Few cardiologists test patients for genetic factors before prescribing Plavix, an anti-blood-clotting drug that fails to prevent blood clots as intended in a quarter of the 4 million Americans prescribed it annually. In 2021, Hawaii won an $834 million case against drugmakers for falsely advertising the drug’s safety and effectiveness for Native Hawaiians, many of whom lack the main enzyme to process it.

While the numbers affected by fluoropyrimidine enzyme deficiency are smaller, and those with the deficiency aren’t at severe risk when using topical forms of the drug for skin cancers, each medically induced death holds weight. At the Dana-Farber Cancer Institute alone, where Carol Rosen was treated among more than 1,000 fluoropyrimidine patients in 2021, her passing prompted action.

Following Rosen’s death, her daughter Lindsay Murray, heartbroken and furious, considered legal action against the hospital and oncologist. However, she chose a different path, writing to Dana-Farber’s chief quality officer, Joe Jacobson, advocating for routine testing. The hospital swiftly implemented a testing system, now covering over 90% of prospective fluoropyrimidine patients. In the first 10 months, they detected around 50 patients with risky gene variants, according to Jacobson.

Dana-Farber employs a Mayo Clinic test that screens for eight potentially harmful variants of the relevant gene. Veterans Affairs hospitals use an 11-variant test, while others typically check for four variants.

It’s evident that different ancestries might require different tests due to the genetic diversity. For example, the worst deficiencies come from different variants in people of African and European descent. There are tests scanning for hundreds of variants, but these take longer and cost more.

These realities hit close to home for Scott Kapoor, an emergency room physician from Toronto, whose brother, Anil Kapoor, died in February 2023 from 5-FU poisoning.

Anil Kapoor, a renowned urologist and surgeon, was a beloved figure whose sudden death from stage 4 colon cancer at age 58 shocked and enraged his family. In Ontario, where Kapoor was treated, the health system had only just begun testing for four gene variants mainly found in European populations. However, the Kapoor siblings, born in Canada to Indian immigrants, carried a gene associated with South Asian ancestry.

Scott Kapoor advocates for wider testing for this defect, especially considering that only about half of Toronto’s population is of European descent. He argues that an FDA-approved antidote to fluoropyrimidine poisoning, available since 2015, should be readily accessible. However, this antidote is effective only within a few days of drug ingestion, while symptoms often manifest later.

Most importantly, Kapoor stresses the need for patients to be informed of the risks. “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 say, ‘I want that test, and I’ll pay for it,’ or they’d say, ‘Reduce the dose.'”

Alan Venook, co-chair of the panel setting colorectal cancer guidelines at the National Comprehensive Cancer Network, has resisted mandatory testing due to what he sees as ambiguous test results that might lead to undertreatment.

Reflecting on a patient who died due to 5-FU toxicity years ago, Venook shares his regret: “But unhelpful information may lead us in the wrong direction.” In September, seven months after his brother’s passing, Kapoor had a chance encounter on a cruise ship near Rome. He met a woman whose husband, Atlanta municipal judge Gary Markwell, had died the year prior after a single dose of 5-FU at 77. Murray, sensing a shift toward mandatory testing, draws attention to Oregon Health & Science University’s $1 million settlement in a suit over an overdose death in 2022. “I think providers are going to feel kind of bullied into a corner,” she predicts. “They’re going to continue to hear from families, and they are going to have to do something about it.

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