Consumption of one glass of grapefruit juice per day may allow cancer patients to take lower doses of certain drugs that are used to fight the disease, suggest researchers.
A new clinical trial – published in Clinical Cancer Research – reveals that an eight ounce glass of grapefruit juice every day could offer cancer patients the same benefits from an anti-cancer drug as they would get from more than three times as much of the drug by itself, by blocking the breakdown (metabolism) of the drug in by the body.
The clinical trial, led by researchers at the University of Chicago Medicine, USA, suggests that a combination of grapefruit juice plus cancer drugs could help patients avoid side effects associated with high doses, in addition to reducing the cost of the medication.
Led by Dr Ezra Cohen, the research team show consumption of grapefruit juice can slow the body's metabolism of sirolimus – a drug that is approved for transplant patients, but may also help those with cancer.
"Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs," explained Cohen, "but this has long been considered an overdose hazard.
“We wanted to see if grapefruit juice can be used in a controlled fashion to increase the availability and efficacy of sirolimus," he said.
The team reveal that cancer patients who drank grapefruit juice increased sirolimus levels by 350%.
"This is the first cancer study to harness this drug-food interaction," the authors note.
Cohen and colleagues organised three simultaneous phase-1 clinical trials of sirolimus. Patients received only sirolimus, sirolimus plus ketoconazole (a drug known to slow the metabolism of other drugs), or sirolimus plus grapefruit juice.
They team enrolled 138 patients with incurable cancer and no known effective therapy.
Initially patients taking only sirolimus were given very low doses – with the amounts gradually increasing as the study progressed. This was done to see how much of the drug was required to reach targeted levels, say the authors, who noted that they wanted to ensure that patients got the greatest anti-cancer effect with the fewest side effects.
They found the optimal cancer-fighting dose for those taking sirolimus alone was about 90 mg per week. Though noted that the drug caused ‘serious’ side effects – including nausea and diarrhea – at doses above 45 mg.
Participants taking sirolimus plus ketoconazole, needed only 16 mg per week to maintain the same levels of drug in the blood, whilst those taking sirolimus plus grapefruit juice required 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, the authors said.
"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,” they said.
Because different people produce varied amounts of the enzymes that break down sirolimus, the effect of grapefruit juice can vary, say the authors. However they suggest that tests of enzyme levels may be able to predict how an individual patient will respond.
The team also highlighted that received support from the US National Institutes of Health for the study – and not from any pharmaceutical company – saying that dose-finding studies are "not necessarily profitable" for pharmaceutical companies; particularly, they add, if the study outcome suggests lower doses than those recommended by the manufacturer after the drug has been approved and priced.
Source: Clinical Cancer Research
Published online ahead of print, doi: 10.1158/1078-0432.CCR-12-0110
“Phase I Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients”
Authors: Ezra E.W. Cohen, Kehua Wu, Christine Hartford, Masha Kocherginsky, Kimberly Napoli Eaton, Yuanyuan Zha, et al