"Personalized" Chemotherapy

A new study by a team of University of Michigan researchers is focusing on ways to tailor chemotherapy doses for individual patients in an attempt to both maximize their effectiveness as well as minimize side effects.

Chemotherapy is the treatment of cancer with drugs that can destroy cancer cells. The amount of chemotherapy given is most often based on a patient's height and weight. But this method does not always lead to the best dose for individual patients.

"The problem with that approach is it doesn't take into account an individual's metabolism of chemotherapy," says Michigan's Dr. Anne Schott, "which could vary greatly depending on what medicines they are on, what their heart function is, what their liver function is, and what their kidney function is."

Schott's team is trying to address the problem by individually tailoring doses for different patients with results from the Erythromycin Breath Test-a test that can determine how a patient's body breaks down the antibiotic erythromycin. Erythromycin is metabolized in the same way as many chemotherapy drugs, by the enzyme CYP3A4.

"We're using the Erythromycin Breath Test to tell us how fast an individual will metabolize other drugs that use the same enzyme," Schott explains. "In the study we're conducting, we're looking at the breast cancer drug Taxotere, which uses that same enzyme, to tell us how to dose the chemotherapy drug."

With the Erythromycin Breath Test, a patient gets an injection of a very small and safe amount of radioactive erythromycin. After they get the injection, they wait 20 minutes for the drug to be metabolized and then they blow air out into a bag. From there, doctors can measure traces of carbon dioxide in their breath. Carbon dioxide is one of the chemicals produced when erythromycin is broken down by the body.

"By using the Breath test, we can actually pick a dose of Taxotere that's specific for the individual, not just based on their height and weight," Schott says. This is important, she adds, because chemotherapy drugs can harm healthy cells, causing side effects. With the use of tailored doses of chemotherapy drugs, it is hoped that patients will be less likely to experience those side effects.

Although the drug Taxotere is being testing in the current study, other chemotherapy drugs are not being ruled out, Schott adds. "We've chosen Taxotere as really a proof of the principle that this sort of tailoring will work. But once this study is completed, we will expand to include drugs which have the same kind of metabolism."

SOURCE:
University of Michigan Comprehensive Cancer Center (www.cancer.med.umich.edu)

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