Reaction to Caffeine Used to Gauge Cancer Drug Dose

Doctors said Monday that they have found a way to figure out the safest and most effective dose of chemotherapy to treat cancer--by measuring the body’s response to the caffeine in a cup of coffee.

So far, the new technique works for only one experimental cancer medicine, but scientists are looking for similar tests that will help them tailor treatment more precisely.

The goal is to allow physicians to give people enough cancer medicine to destroy their tumors without triggering life-threatening side effects.

Dr. Mark J. Ratain of the University of Chicago described his findings with the coffee test at a meeting of the American Cancer Society.

The coffee test will allow doctors to pick the best dose of amonafide, a promising experimental medicine that is being studied for use against cancer of the breast, uterus and prostate.

“We would like to maximize the dose to maximize response,” said Ratain. “We know that the more chemotherapy we give, the better the chance of benefit. We are limited by toxicity.”

Currently, doctors pick doses of chemotherapy based on the patients’ height and weight. However, there are great differences in how people respond to amonafide, as there are to many other drugs. A dose that causes no side effects for one person may kill another.

“The average patient does not exist,” he said. “Everybody is more sensitive or less sensitive.”

Amonafide is broken down in the body through a process known as acetylation. People who are fast acetylators produce high levels of a substance called N-acetyl-amonafide, which is highly toxic.

Therefore, people who are slow acetylators should receive higher doses, and those who are fast acetylators should get less. But until recently, there was no way to figure this out in advance.

Caffeine, the chemical that gives coffee its kick, is acetylated the same way as amonafide. So by using urine analysis that measures how quickly people break down the caffeine in a cup of coffee or a can of caffeinated cola, doctors can estimate how their bodies will respond to the cancer drug.

“It appears that when the drug is given properly, the response rate can be quite high,” Ratain said.

In testing on 18 cancer patients, Ratain found that 11 were slow acetylators and seven were rapid acetylators. All were given standard doses of the drug. None of the slow acetylators had serious side effects, but three of the fast acetylators had life-threatening reactions.