Research points to potentially cheaper targeted cancer treatment

In collaboration with the Press Association

Sirolimus, a cheap and widely available drug used to treat transplant patients, is suitable for further testing to treat cancer when combined with grapefruit juice, according to a preliminary clinical trial in the US.

It could provide "substantial cost savings" if shown to be as effective as related drugs such as evirolimus (Afinitor), say the study's authors.

Researchers at the Universities of Chicago and Texas carried out a trial involving 138 people with advanced cancer, to work out how the body handles the drug, which is also known as rapamycin.

They found that combining it with grapefruit juice, or with a drug called ketoconazole, caused blood levels of the drug to rise to potentially effective levels, with relatively few side effects.

"Grapefruit juice, and drugs with a similar mechanism, can significantly increase blood levels of many drugs," said study director and cancer specialist Dr Ezra Cohen, "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."

Sirolimus was discovered in 1975. It works by targeting a cell protein called mTOR, which is involved in cancer.

But it can be rapidly broken down and so requires large doses, and was thus thought to be unsuitable as a cancer treatment.

As a result, cancer drug developers have used it as a starting point to develop more advanced compounds, and these drugs are now licensed for use.

The study split cancer patients into three groups: those receiving just sirolimus; those given sirolimus with grapefruit juice; and those given sirolimus with ketoconazole.

Those taking sirolimus with grapefruit juice needed less than half the amount of those taking the drug alone to achieve the same levels in their blood, whist avoiding side effects such as nausea and diarrhoea.

Those taking sirolimus with ketoconazole needed about a sixth the amount.

Despite ketoconazole's effectiveness, grapefruit juice has the advantage that it is non-toxic, with no risk of overdose.

Commenting on the research, Liz Woolf, who runs Cancer Research UK's patient information website, said the results opened a new avenue for future research.

"These early results are interesting and suggest that sirolimus could be a cheaper alternative to several drugs already on the market.

"Since grapefruit juice contains chemicals that can raise or lower the amount of certain drugs in the body, cancer patients are sometimes asked to avoid drinking it during treatment. The research showed that sirolimus didn't seem to cause serious side effects when taken with the juice, so it can be tested in further trials."

The research is published in Clinical Cancer Research.

Copyright Press Association 2012

References

Cohen E.E.W. et al, Phase I Studies of Sirolimus Alone or in Combination with Pharmacokinetic Modulators in Advanced Cancer Patients, (2012) Clin Can Res DOI: 1078-0432.CCR-12-011