A relatively simple technique, pioneered by a
North Carolina physician, can distinguish between patients who can
metabolize docetaxel (Taxotere) normally and those who need to
receive lower doses for safety, according to a recent study.
Researchers say the approach might work for other chemotherapeutic
agents and perhaps other noncancer drug treatments as well.
Because of diet, genetics, and other factors, some people just
metabolize drugs a lot more slowly, said Paul B. Watkins, MD,
professor of medicine and director of the Verne S. Caviness General
Clinical Research Center at the University of North Carolina at
Chapel Hill School of Medicine. As a result, the recommended
dose of many chemotherapies will predictably make about 10% of
patients very ill, and 1% or 2% of patients may die as a direct
result of the treatment. Conversely, patients whose livers
rapidly clear a given chemotherapy may not get a dose strong enough
to be effective against their cancer, he said.
A report on the new study appears in the April issue of Clinical
Cancer Research. Besides Dr. Watkins, the study was authored by Drs.
JoAnn Hirth, Myla Strawerman, Anne Schott, and Laurence Baker of the
University of Michigan.
Carbon Dioxide Levels Give Clues
Investigators took blood samples from 21 cancer patients several
times over 24 hours to determine how fast their livers cleared the
drug docetaxel and compared those results with measurements of the
patients breath. In the 20-minute breath test, which Dr.
Watkins developed and patented, doctors gave patients a trace dose of
the common antibiotic erythromycin and measured the amount of carbon
dioxide they exhaled.
Higher concentrations of exhaled carbon dioxide meant that patients
were metabolizing erythromycin more quickly, and lower concentrations
meant they were metabolizing it more slowly, Dr. Watkins said. The
liver uses the same enzyme system, or pathway, to clear docetaxel as
it does to process erythromycin.
We didnt look at the data until the study was over,
Dr. Watkins said. Among other things, we found that the two
patients who got very ill and had to be hospitalized showed the
lowest test results and the lowest levels of enzyme activity.
Test Shows Promise
In an accompanying editorial, Dr. Jerry M. Collins, director of the
Laboratory of Clinical Pharmacology at the US Food and Drug
Administration, said that the new assay, which builds on a tradition
of using breath tests as indicators of liver function, has numerous
It is rapid, relatively noninvasive, requires only a single
time point, and can be used prospectively before dosing, he
said. Because of the narrow therapeutic range of anticancer
drugs, lowering the likelihood of toxicity in patients at greatest
risk is a useful contribution.
Dr. Watkins said that while it is not proven yet, other forms of
chemotherapy likely employ the same pathway measured by his breath
test. Even if they do not, comparable simple tests probably can be
developed that will help protect patients treated with drugs
metabolized via different enzymes.