The treatment of gastrointestinal stromal tumor, or GIST, even in its advanced metastatic stage, has been dramatically improved with two oral targeted drugs – imatinib (Gleevec) and sunitinib (Sutent). To date, these have represented the only two FDA-approved treatments with the proven ability to control GIST. However, in more than 85 percent of patients, GIST becomes resistant to these drugs after seven years and the disease worsens with fatal results.
The new study, whose results are being published in the Lancet, demonstrated that the oral drug regorafenib, which inhibits several cancer-promoting kinase enzymes, was able to control GIST for nearly four months longer than placebo in patients for whom Gleevec and Sutent were no longer effective, a result that was highly significant statistically.
"When added to best supportive care, regorafenib significantly improves disease control, as measured by progression-free survival time in patients with GIST after progression which represents failure of all other therapies," said George Demetri, MD, of Dana-Farber, principal investigator of this clinical trial.
Demonstrating the aggressive nature of this resistant disease, the study found that tumors objectively grew in less than a month, on average, in GIST patients who were initially randomized to receive a placebo. The study's "cross-over" design made it possible to treat those patients whose tumors grew, and 85 percent of the patients initially on placebo were able to receive regorafenib, which then controlled the disease in these patients as well.
Because of the study's cross-over design, Demetri said, it was not expected to prove that the patients initially randomized to receive regorafenib survived longer – the researchers would have had to withhold the drug from the placebo patients to demonstrate that difference. "But there is no question that people are living longer" with regorafenib treatment, he said, based on the results of this trial.
An application to have regorafenib approved for use in resistant GIST is under an accelerated review by the Food and Drug Administration, Demetri said.
GIST is a rare form of sarcoma that develops in the gastrointestinal tract, mainly in the stomach and small intestine. GIST is estimated to affect more than 5,000 people per year in the United States and about 8,000 in Europe.
Regorafenib is a novel rationally designed drug manufactured by Bayer HealthCare Pharmaceuticals that was FDA-approved in September 2012 to treat metastatic colon cancer after failure of standard chemotherapy. It blocks several cancer-promoting enzymes called kinases, which spur runaway growth in GIST and other cancers.
The phase 3 international trial involved 199 treatment-resistant GIST patients at 57 hospitals in 176 countries. Of the 199 patients, 133 received a regorafenib pill daily for three weeks followed by a one-week break, while 66 received a matching placebo. The patients were monitored for at least one year after the trial began.
As for other targeted therapies, the drug did not often shrink tumors but controlled the disease for an average of 4.8 months before it progressed, while patients in the placebo group experienced less than one month (0.9 month) before the disease worsened. There was a high rate of adverse effects including high blood pressure, fatigue, diarrhea, and redness, swelling, numbness and peeling of skin on the hands and feet. These side effects were managed by reducing or interrupting the regorafenib treatment, the report said.
A companion report in The Lancet said that the drug had a "modest" benefit in patients with metastatic colon cancer. A commentary by David Cunningham, MD, of the Royal Marsden Hospital in England, said, "In the relatively rare GIST, the case for routine use of this drug in patients following failure of existing treatments is strong."
Demetri added "We know that regorafenib can inhibit many of the mutated proteins and abnormal signals that cause this cancer, and the next step will be to investigate the molecular mechanisms by which this new treatment can control GIST after resistance appears to other 'targeted therapy' drugs for this aggressive malignancy."
The clinical trial was supported, in part, by Bayer HealthCare Pharmaceuticals, as well as the Ludwig Center at Dana-Farber/Harvard Cancer Center.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Children's Hospital Boston as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Twitter: @danafarber or Facebook: facebook.com/danafarbercancerinstitute.
More articles from Health and Medicine:
New concussion data: 2 biomarkers better than 1
19.06.2013 | University of Rochester Medical Center
Tackling a framework for surgical innovation
19.06.2013 | Weill Cornell Medical College
- Biological fermentation process converts CO and CO2 into bioethanol and platform chemicals
- Process uses energy contained in steel plant off-gases
- Ten-year co-operation to develop and market integrated environmental solutions for the steel industry worldwide
Siemens Metals Technologies and LanzaTech have signed a ten-year co-operation agreement to develop and market integrated environmental solutions for the steel industry worldwide. The collaboration will utilize the ground-breaking fermentation technology developed by LanzaTech transforming carbon-rich off-gases generated by the steel industry into low carbon bioethanol and other platform chemicals. ...
Novel application of 3D printing could enable the development of miniaturized medical implants, compact electronics, tiny robots, and more
3D printing can now be used to print lithium-ion microbatteries the size of a grain of sand. The printed microbatteries could supply electricity to tiny devices in fields from medicine to communications, including many that have lingered on lab benches for lack of a battery small enough to fit the ...
... two engines aircraft project “Elektro E6”.
The countdown has been started for opening the gates again for the worldwide leading aviation and space event in Le Bourget, Paris from June 17th - 23rd, 2013.
EADCO & PC-Aero will present at the Paris Air Show in Hall H4 booth F-7 their new future aircraft and innovative project: ...
Siemens scientists have developed new kinds of ceramics in which they can embed transformers.
The new development allows power supply transformers to be reduced to one fifth of their current size so that the normally separate switched-mode power supply units of light-emitting diodes can be integrated into the module's heat sink.
The new technology was developed in cooperation with industrial and research partners who ...
Cheaper clean-energy technologies could be made possible thanks to a new discovery.
Led by Raymond Schaak, a professor of chemistry at Penn State University, research team members have found that an important chemical reaction that generates hydrogen from water is effectively triggered -- or catalyzed -- by a nanoparticle composed of nickel and phosphorus, two inexpensive elements that are abundant on Earth. ...
19.06.2013 | Life Sciences
19.06.2013 | Agricultural and Forestry Science
19.06.2013 | Studies and Analyses
14.06.2013 | Event News
13.06.2013 | Event News
10.06.2013 | Event News