Washington: Drinking grapefruit juice lets patients derive the same benefits from low dose of an anti-cancer drug as they would get from more than three times as much of the drug by itself, according to a new clinical trial.
The combination could help patients avoid side effects associated with high doses of the drug and reduce the cost of the medication.
Researchers at the University of Chicago Medicine study the effects that foods can have on the uptake and elimination of drugs used for cancer treatment.
In the study, they found that eight ounces a day of grapefruit juice can slow the body’s metabolism of a drug called sirolimus, which has been approved for transplant patients but may also help many people with cancer.
Sirolimus was the first of a series of drugs, known as mTOR inhibitors, that were developed to prevent rejection of transplanted organs but that also have anti-cancer effects.
Patients who drank eight ounces a day of grapefruit juice increased their sirolimus levels by 350 percent. A drug called ketoconazole that also slows drug metabolism increased sirolimus levels by 500 percent.
“Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs,” said study director Ezra Cohen, MD, a cancer specialist at the University of Chicago Medicine, “but this has long been considered an overdose hazard. Instead, we wanted to see if grapefruit juice could be used in a controlled fashion to increase the availability and efficacy of sirolimus.”
Grapefruit juice’s pharmaceutical prowess stems from its ability to inhibit enzymes in the intestine that break down sirolimus and several other drugs. The effect begins within a few hours of what the researchers refer to as “grapefruit juice administration.” It wears off gradually over a few days.
Cohen and colleagues organized three simultaneous phase-1 trials of sirolimus. Patients received only sirolimus, sirolimus plus ketoconazole, or sirolimus plus grapefruit juice. They enrolled 138 patients with incurable cancer and no known effective therapy.
The first patients started with very low sirolimus doses, but the amounts increased as the study went on, to see how much of the drug was required in each setting to reach targeted levels, so that patients got the greatest anti-cancer effect with the least side effects.
The optimal cancer-fighting dose for those taking sirolimus was about 90 mg per week. At doses above 45 mg, however, the drug caused serious gastrointestinal problems, such as nausea and diarrhea, so patients taking sirolimus alone switched to 45 mg twice a week.
The optimal doses for the other two groups were much lower. Patients taking sirolimus plus ketoconazole, needed only 16 mg per week to maintain the same levels of drug in the blood. Those taking sirolimus plus grapefruit juice, needed between 25 and 35 mg of sirolimus per week.
Although ketoconazole produced a slightly stronger drug-retention effect, grapefruit juice has the advantage that it is non-toxic, with no risk of overdose.
Because different people produce varied amounts of the enzymes that break down sirolimus, the effect of grapefruit juice can vary, but tests of enzyme levels may be able to predict how an individual patient will respond.
The findings were published in August in Clinical Cancer Research.