For two decades, pharmacists have pasted DO-NOT-TAKE-WITH-GRAPEFRUIT-JUICE stickers on various pill bottles because it can interfere with the enzymes that break down and eliminate certain drugs. This interference makes the drugs more potent. In data presented at the AACR 100th Annual Meeting 2009, the Chicago researchers examine ways to exploit this fruit's medication-altering properties.
"Grapefruit juice can increase blood levels of certain drugs three to five times," said study director Ezra Cohen, MD, 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 said.
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 (Citius paradisi), 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 (28%) had stable disease, with little or no tumor growth. One patient (4%) had a partial response, with the tumor shrinking by about 30 percent. That patient is still doing well more than a year after beginning the trial.
"My first cancer doctor gave me five years to live," said that patient, Albina Duggan of Bourbonnais, IL. "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 said. "What's not to like?"
Trial subjects do not like the taste of rapamycin. "It's not pleasant," Duggan admitted. 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 said, "seriously curly. I have to adjust to it."
Rapamycin, also known as sirolimus, was originally developed to suppress the immune system, preventing rejection in patients receiving a transplanted kidney. Cancer specialists became interested in the drug when they learned that it disrupted a biochemical pathway involved in the development of the new blood vessels that tumors need to grow. But the drug is expensive and poorly absorbed. Less than 15 percent of rapamycin is absorbed when taken by mouth.
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," said 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 said. "A daily glass of juice could lower the cost by 50 percent."
The study will be presented at the AACR's 100th Annual Meeting in Denver in a session on "Late-Breaking Research: Clinical Research 1: Phase I-III Clinical Trials," Poster Section 27, from 1 to 5 p.m. on Monday, April 20, 2009.
John Easton | EurekAlert!
WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf
First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.
Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...
A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.
Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
18.05.2018 | Power and Electrical Engineering
18.05.2018 | Information Technology
18.05.2018 | Information Technology