Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New drug overcomes resistance in patients with rare sarcoma

22.11.2012
A new targeted drug demonstrated its ability to control metastatic gastrointestinal stromal tumor, an uncommon and life-threatening form of sarcoma, after the disease had become resistant to all existing therapies, report investigators at Dana-Farber Cancer Institute who led the worldwide clinical trial.

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.
Contact:
Robbin Ray
Richard Saltus
617-632-4090

Robbin Ray | EurekAlert!
Further information:
http://www.dfci.harvard.edu
http://www.dana-farber.org/

More articles from Health and Medicine:

nachricht How cancer metastasis happens: Researchers reveal a key mechanism
19.01.2018 | Weill Cornell Medicine

nachricht Researchers identify new way to unmask melanoma cells to the immune system
17.01.2018 | Duke University Medical Center

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Thanks for the memory: NIST takes a deep look at memristors

22.01.2018 | Materials Sciences

Radioactivity from oil and gas wastewater persists in Pennsylvania stream sediments

22.01.2018 | Earth Sciences

Saarland University bioinformaticians compute gene sequences inherited from each parent

22.01.2018 | Life Sciences

VideoLinks Wissenschaft & Forschung
Overview of more VideoLinks >>>