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!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Physics and Astronomy
28.03.2017 | Health and Medicine
28.03.2017 | Life Sciences