Dutch study makes chemotherapy safer: ‘We can take away a lot of suffering’

People with colon or pancreatic cancer have a much smaller risk of side effects after chemotherapy if they first undergo a certain DNA test. This is apparent from a large-scale study by Maarten Deenen, hospital pharmacist at the Catharina Hospital in Eindhoven.

By first subjecting each patient to such a test, it is possible to recognize a mutation in the so-called UGT1A1 gene. This mutation ensures that chemotherapy drugs, in this case the drug irinotecan, are broken down less well by the body. The mutation is therefore responsible for a greater risk of severe side effects.

A doctor’s dilemma

Oncologist Geert-Jan Creemers of the Catharina Hospital is pleased with the findings of his Eindhoven colleague Deenen. He always finds it terrible when a patient with colon or pancreatic cancer responds badly to chemotherapy and gets serious side effects. Severe diarrhea where liters of fluid are lost per day and a rapid decline in the immune system are no exception. Patients are then extra sensitive to infections that can quickly become life-threatening.

“It is always a dilemma for a doctor who administers chemotherapy. You are using a harmful agent to destroy tumor cells, but there is a risk of harming the patient himself.”

But doctors can now better estimate these risks. Deenen investigated whether patients with the problematic mutation suffer significantly less from side effects if they receive a lower dose of the drug. “That turned out to be the case. At the same time, the drug does not lose effectiveness in fighting the disease.”

Emergence of personalized treatments

Marcel Verheij, professor of radiotherapy at Radboudumc and chair of the Oncology SONCOS platform of the Federation of Medical Specialists, says that this approach is a good example of the rise of personalized treatments.

“Previously, chemotherapy was more of a ‘one size fits all’ character. But thanks to such genetic analysis, we can not only look at the make-up of tumor cells and their susceptibility to a specific treatment at the molecular level, but also see how the genetics of the patient plays a role in the breakdown of drugs and the development of side effects.”

According to Verheij, the effectiveness of chemotherapy is largely determined by such genetic relationships. “If you know those, you as a doctor can make the dosages very specific and person-oriented.”

One of the most common cancers

“We take away a lot of suffering with this,” says researcher Deenen. “With such severe diarrhea you simply have to be admitted to a hospital. In addition, colorectal cancer is diagnosed in about 12,000 people every year, making it one of the most common types of cancer in the Netherlands. Pancreatic cancer is one of the most deadly.”

Deenen is convinced that the treatment method proposed in his research will soon become part of the (international) standard. The research results have now been subjected to critical scrutiny by medical colleagues – a so-called peer review – and published in the scientific journal European Journal of Cancer.

“The scientific and medical committees use these kinds of publications to evaluate and adapt treatment guidelines,” says Deenen. “During a conference of the Dutch Association for Medical Oncology, 71 percent of oncologists said they wanted to introduce this method as soon as possible.”

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