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Grapefruit Juice Allows Lower Dose of Cancer Drug

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Many foods can have an effect on the uptake and elimination of drugs used for cancer treatment. In a study performed by researchers at the University of Chicago Medicine and published in August in Clinical Cancer Research, data show that 8 ounces a day of grapefruit juice can slow the body’s metabolism of sirolimus, a drug that may help patients with cancer.

“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 can be used in a controlled fashion to increase the availability and efficacy of sirolimus.”

For the patients who drank 8 ounces per day of grapefruit juice, sirolimus levels increased 350%. Study results showed that another drug, ketoconazole, also slowed drug metabolism and increased sirolimus levels by 500%.

For the study, Cohen and colleagues enrolled 138 patients with incurable cancer and no known effective therapy. Researchers organized 3 simultaneous phase 1 trials of sirolimus in which patients received either sirolimus alone, sirolimus plus ketoconazole, or sirolimus plus grapefruit juice.

In order to achieve the greatest anticancer effect and the fewest side effects, the first patients started with very low sirolimus doses. Amounts gradually increased as the study progressed, so researchers could determine how much of the drug was required to reach targeted levels.

The optimal cancer-fighting dose for those taking sirolimus was about 90 mg per week. However, the drug caused serious gastrointestinal problems (nausea and diarrhea) at doses greater than 45 mg. Therefore, patients taking sirolimus alone switched to 45 mg twice a week.

The optimal doses for the other 2 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.

About 30% of patients in the 3 trials had stable disease. However, no patients had a complete response. One patient receiving grapefruit juice had significant tumor shrinkage that lasted for more than 3 years.

Although a slightly stronger drug-retention effect was observed with ketoconazole, grapefruit juice is non-toxic and has no risk of overdose. “Therefore, we have at our disposal an agent that can markedly increase bioavailability (in this study by approximately 350%) and, critically in the current environment, decrease prescription drug spending on many agents metabolized by P450 enzymes,” the authors wrote.

The number of enzymes present that break down sirolimus can differ among patients, and thus the effect of grapefruit juice can vary. However, enzyme level testing may predict how an individual patient will respond.

“The variation in potency of the grapefruit juice itself may be far greater than the variation in the enzymes that break down sirolimus,” Cohen said. An early version of the study used canned grapefruit juice, but tests of the product found it lacked the active ingredients. So, a frozen concentrate was used instead.

Source: University of Chicago Medicine.