Grapefruit Juice Helps Anti-Cancer Drug Work Better
A new clinical trial published in the August edition of Clinical Cancer Research has revealed that cancer patients who drink one glass of grapefruit juice per day achieve the same benefits from an anti-cancer drug as they would get from more than three times as much of the drug by itself. It could also help patients to avoid side effects linked to high doses of the drug, whilst reducing medication costs at the same time.
Scientists from Chicago’s University of Medicine have researched the potential impact of foods on the uptake and elimination of drugs used for cancer treatment and discovered that eight ounces a day of grapefruit juice can slow the body’s metabolism of a drug called sirolimus, an approved drug for transplant patients, which may also be of benefit to many suffering from cancer.
They observed that sirolimus levels were raised by 350% in patients who drank eight ounces of grapefruit juice per day, and by 500% in those taking ketoconazole, a drug that slows down the metabolism.
Director of the study Ezra Cohen, MD, a cancer specialist at the University of Chicago Medicine said:
“Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs, 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 can inhibit enzymes in the intestine, which break down sirolimus and several other drugs. The effect starts within a few hours of what the researchers refer to as “grapefruit juice administration,” and gradually subsides over a few days.
Cohen and his team conducted three simultaneous phase-1 trials of sirolimus in which 138 patients with incurable cancer and no known effective therapy either received only sirolimus or sirolimus plus ketoconazole, or sirolimus plus grapefruit juice. To maximize the greatest anti-cancer effect with the least side effects, the team started the first patients on very low doses of sirolimus, which they increased as the study progressed in order to assess the required amount of drug in each setting to reach targeted levels.
They noted that the best cancer-fighting dose in the sirolimus alone group consisted of around 90 mg per week, although they observed that doses above 45 mg caused serious gastrointestinal problems like diarrhea and nausea, and therefore switched this group of patients back to 45 mg twice a week. In contrast, the optimal doses to maintain the same levels of drug in the blood for the sirolimus plus ketoconazole group was 16 mg per week and that of the sirolimus plus grapefruit juice group between 25 and 35 mg per week, which is considerably lower.
The team comments: “This is the first cancer study to harness this drug-food interaction.”
Although none of the study participants showed a complete response, in around 30% of patients the cancer had stabilized, meaning the disease did not progress and one patient in the grapefruit juice group showed a partial response in form of a substantial tumor shrinkage, which lasted for over three years. In comparison to the slightly stronger drug-retention effect of ketoconazole, the advantage of grapefruit juice is that it is non-toxic with no risk of overdose.
The researchers declare:
“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.”
Sirolimus was one of the first mTOR inhibitors developed to prevent rejection of transplanted organs, which also has anti-cancer effects. Being the first drug of its class it was therefore also the first to come off patent, which made the drug more economical. The team comments: “Further cost savings could be realized “by combining the drug with agents that inhibit its metabolism.”
The amount of enzymes produced that break down sirolimus varies from person to person, meaning that the effect of grapefruit juice is also subject to variation. However, testing enzyme levels could predict responses in individual patients.
Cohen said: “The variation in potency of the grapefruit juice itself may be far greater than the variation in the enzymes that break down sirolimus.”
At the start of the study, the team used canned grapefruit juice but tests revealed insufficient active ingredients and the team therefore switched to use a frozen concentrate product.
The team highlights the fact that they only received support from the National Institutes of Health for their study, but not from any pharmaceutical company, saying that dose-finding studies are “not necessarily profitable” for pharmaceutical companies, particularly if the study outcome suggests lower doses than those recommended by the manufacturer after the drug has been approved and priced.
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