A glass of grapefruit juice lowers the amount of cancer drug
Drinking grapefruit just allows the same benefits from low dose drug as high dose
Researchers from the University of Chicago Medicine study the effects that food on the uptake and elimination of drugs used for cancer treatment. According to this new clinical trial the combination could help patients avoid side effects resulting from high doses of the drug and it lowers the cost of medication.View slideshow: Cancer fighting foods
The researchers found that just eight ounces a day of grapefruit juice can slow the body’s metabolism of the drug sirolimus that belongs to a group of immunosuppressive agents that is used to lower the body’s natural immunity in patients who receive transplants but may also help people with cancer.
Patients who drank 8 ounces a day of grapefruit juice increased their sirolimus levels by 350%. A drug called ketoconazole that also slows drug metabolism increased sirolimus levels by 500%.
Grapefruit juice prevents enzymes in the intestines break down sirolimus and several other drugs begin within a few hours of consumption and wears off over a few days.
Dr. Ezra Cohen, MD, associate professor of medicine and associate director for education, University of Chicago Comprehensive Cancer Center, study director and fellow associates 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 optimum dosage for those taking sirolimus was around 90mg a week. Doses above 45 mg, the drug caused serious gastrointestinal problems, such as nausea and diarrhea, so patients taking sirolimus alone switched to 45 mg twice a week.
For the other two groups the optimal dosages 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.
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. As the first of its class, it was also the first to come off patent, making it less costly. "Further cost savings," the authors suggest, could be realized "by combining the drug with agents that inhibit its metabolism."
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.
Dr. Cohen stated "The variation in potency of the grapefruit juice itself may be far greater than the variation in the enzymes that break down sirolimus.”
These findings were published in August in Clinical Cancer Research.
This is not the first time Dr. Cohen looked at the effects of grapefruit juice boosting drugs anti-cancer effects.
In 2009, in a small early clinical trial Dr. Cohen and associates found that combing eight ounces of grapefruit juice with the drug rapamycin can increase drug levels, allowing lower doses to be used. Rapamycin is also known as sirolimus.
According to Dr. Cohen that trial had been designed to test "whether we could use this to boost rapamycin's bioavailability to the patient's advantage, to determine how much the juice altered drug levels, and to assess its impact on anti-cancer activity and side effects.”
The study followed 28 patients with advanced solid tumors, for which there is no effective treatment. The dose of the drug increased with each group of five patients, from 15 milligrams up to 35. Patients took the drug by mouth, as a liquid, once a week.
At the start of week two immediately after taking rapamycin they consumed a glass of grape fruit juice and also consumed the juice once daily for the rest of the week.
Among the participants, 25 had remained in the study long enough to be evaluated. Among the 25 participants, 28% had stable disease with little or no tumor growth. One patient had a partial response with tumor shrinking around 30% and it was reported the patient was still doing well one year after the trial.
Dr. Cohen had stated "A daily glass of juice could lower the cost by 50 percent."
This study had been presented at AACR's 100th Annual Meeting in Denver in a session on "Late-Breaking Research: Clinical Research 1: Phase I-III Clinical Trials.”
Dr. Cohen’s research interest includes discovering how cancers become resistant to existing treatments and overcoming these mechanisms, and discovering ways to combine radiotherapy with novel agents.
Dr. Cohen has developed an expertise in head and neck cancer resulting in lecture invitations at scientific meetings around the world, numerous publications, and prestigious awards. He also serves as editor-in-chief of Oral Oncology.