cancer

Grapefruit boosts cancer drug’s potency

grapefruit

For two decades, pharmacists have pasted grapefruit warnings on prescription bottles because the fruit’s juice can interfere with enzymes that break down and eliminate certain drugs, making the drugs more potent.

U. CHICAGO (US)—Combining grapefruit juice with the anticancer drug rapamycin appears to increase the drug’s strength. The combination seems effective in treating various types of cancer and could allow for lower doses of the drug, according to a study by researchers at the University of Chicago Medical Center.

For two decades, pharmacists have pasted grapefruit warnings on prescription bottles because the fruit’s juice can interfere with enzymes that break down and eliminate certain drugs, making the drugs more potent. Chicago researchers began looking for ways to exploit grapefruit’s medication-altering properties.

“Grapefruit juice can increase blood levels of certain drugs three to five times,” says study director Ezra Cohen, a cancer specialist at the University of Chicago Medical Center. “This has always been considered a hazard. We wanted to see if, and how much, it could amplify the availability, and perhaps the efficacy of rapamycin, a drug with promise for cancer treatment.”

This trial was 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,” he adds.

Clinical tests
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. Beginning in week two, they washed it down with a glass of grapefruit juice, taken immediately after the rapamycin and then once a day for the rest of the week.

Twenty-five participants remained in the study long enough to be evaluated. Seven of those 25 had stable disease, with little or no tumor growth. One patient, Albina Duggan, had a partial response, with the tumor shrinking by about 30 percent. Duggan is still doing well more than a year after beginning the trial.

One mother’s story
“My first cancer doctor gave me five years to live,” she says. “That time runs out next July.”

Duggan, mother of four, has a rare cancer, an epitheliod hemangioendothelioma that originated in the liver and subsequently spread to two vertebrae in the neck and to the lymph nodes. She had surgery and radiation therapy and was evaluated for a liver transplant, but evidence of cancer beyond the liver made her ineligible for a transplant. She “shopped around” for other therapies and was able to keep the disease in check for a year with sorafenib, a drug approved for kidney and liver cancers.

After a year of stable disease, however, her tumor began growing again and she had to look for an alternative therapy. Her doctors at the University of Chicago offered three clinical trials. The most appealing to her was the rapamycin plus grapefruit juice study. She took her first dose March 11, 2008, and is still on the drug-juice combination.

“My tumor is smaller and it’s no longer growing. I feel fine. I can do whatever I like and I have no real side effects,” she says. “What’s not to like?”

Trial subjects do not like the taste of rapamycin. “It’s not pleasant,” Duggan admits. She has also tired of grapefruit juice.

Many patients in the study did report side effects. More than half experienced elevated blood sugar levels, diarrhea, low white blood cell counts or fatigue.

Duggan, more fortunate than most, has had milder side effects, including fragile toe and finger nails and curly hair. “I now have very curly hair,” she says, “seriously curly. I have to adjust to it.”

Big effect, low cost
This study showed that substances known a furanocoumarins, plentiful in some forms of grapefruit juice, can decrease the breakdown of rapamycin. This makes the drug reach higher levels in the bloodstream, two to four times the levels seen without a juice boost, and thus increases the amount of the drug that reaches its targets.

“That means more of the drug hits the target, so we need less of the drug,” explains Cohen.

Many of the newer cancer medications, precisely focused on specific targets, are now taken as pills rather than intravenously. Some of these drugs, including rapamycin, can cost thousands of dollars a month. Hence, “this is an opportunity for real savings,” Cohen adds. “A daily glass of juice could lower the cost by 50 percent.”

University of Chicago news: http://news.uchicago.edu

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