Waiting to exhale

A simple breath test can help identify patients most likely to suffer severe side effects of chemotherapy with docetaxel, one of the most widely used anticancer drugs. This is a result of a small study published in the April Clinical Cancer Research.

The new test measures the activity of an enzyme known as cytochrome p450 3A4 (CYP 3A4), which breaks down, or metabolizes, docetaxel and many other drugs, says Paul B. Watkins of the University of North Carolina-Chapel Hill School of Medicine.

“Because of diet, genetics, and other factors, some people just metabolize drugs a lot more slowly,” he says. “As a result, the recommended doses of many chemotherapies will predictably make about 10 percent of patients very ill, and 1 or 2 percent of patients may die as a direct result of the treatment.” The breath test may change that by helping doctors identify patients who should get lower or higher doses than doctors would prescribe based on body weight alone, says Watkins. The test measures the concentration of radioactive carbon dioxide exhaled by a person 20 minutes after being given radioactively labeled erythromycin, an antibiotic that CYP 3A4 breaks down.

Breathing out low concentrations of radioactive carbon dioxide indicates that the enzyme is working relatively slowly. In people with slow-acting CYP 3A4, the cancer drug will accumulate to toxic levels at lower doses.

In a study of 21 cancer patients, the breath test predicted about two-thirds of the variability in people’s ability to break down docetaxel, as measured by blood tests. The two patients in the study who had to be hospitalized for side effects from docetaxel had the lowest scores on the breath test, Watkins says.

He and his colleagues plan to give the breath test to another 100 people with cancer and adjust the patients’ doses of docetaxel accordingly to minimize side effects.