Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Everolimus prolongs progression-free survival for patients with neuroendocrine tumors

30.11.2011
Combination treatment with octreotide shows improved results in tumors associated with carcinoid syndrome

Combination treatment with everolimus, an inhibitor of the mammalian target rapamycin (mTOR), and octreotide has shown to improve progression-free survival for patients with advanced neuroendocrine tumors and a history of carcinoid syndrome, according to researchers at The University of Texas MD Anderson Cancer Center.

Results of the international, randomized, placebo-controlled Phase III study were published today in the journal Lancet.

The treatment combination of everolimus and octreotide long-acting repeatable (LAR), a somatostatin analogue that has shown antitumor activity, led to a clinically meaningful five-month delay in tumor growth, compared to octreotide alone.

Neuroendocrine tumors, also known as carcinoids, are uncommon tumors arising from various primary sites. Frequently, carcinoids spread to the liver, causing a variety of symptoms termed carcinoid syndrome.

"There are currently no Food and Drug Administration (FDA) approved drugs for oncologic control of most neuroendocrine tumors," said James C. Yao, M.D., associate professor in MD Anderson's Department of Gastrointestinal Medical Oncology. "This research offers a promising option where there were limited options previously."

Dangerous and rare tumors

According to Yao, the number of people diagnosed with neuroendocrine tumors has increased more than five-fold over the past 30 years, from one in 100,000 people per year to 5.25 in 100,000 people per year. Nearly half of patients have regional or distant metastatic disease and 65 percent of those with advanced disease die within five years of diagnosis.

Everolimus, an immunosupressant agent used to prevent rejection of organ transplants, inhibits the mTOR protein, a central regulator of tumor cell division and blood vessel growth in cancer cells. Overaction of mTOR has been implicated in the pathogenesis of neuroendocrine tumors.

Preclinical studies have shown that mTOR inhibition may control growth of neuroendocrine tumors, and an earlier Phase II study at MD Anderson showed promising anti-cancer activity for everolimus in neuroendocrine tumors.

In May of this year, an international randomized Phase III study showed everolimus improved progression-free survival in pancreatic neuroendocrine tumors, a related disease, leading to its FDA approval for treatment of those rare tumors.

Somatostatin analogues, such as octreotide, improve hormone-related symptoms associated with neuroendocrine tumors. Octreotide LAR has also shown antitumor activity, prolonging time to disease progression in patients with certain types of neuroendocrine tumors.

Increase in progression-free survival

The study, named RADIANT-2, enrolled 429 participants with low-grade or intermediate-grade advanced (unresectable locally advanced or distant metastatic) neuroendocrine tumors and a history of carcinoid syndrome. Disease progression had been established by radiological assessment within the past 12 months.

Patients were given either 10 mg per day oral everolimus or placebo, both in conjunction with 30 mg intramuscular octreotide LAR, every 28 days. Treatment was continued until disease progression, withdrawal from treatment because of adverse effects or withdrawal of consent.

Median progression-free survival by was 16.4 months in the everolimus plus octreotide LAR group and 11.2 months in the placebo plus octreotide LAR group.

Side effects were higher but manageable in the combination arm. They included stomatitis (62 percent vs. 14 percent), fatigue (31 percent vs. 23 percent) and diarrhea (27 percent vs. 16 percent).

Next steps

Yao said additional exploratory analyses to adjust for the effect of randomization imbalances will be presented at American Society of Clinical Oncology (ASCO) gastrointestinal annual meeting in 2012.

"We are working with industry sponsor [Novartis] to develop a confirmatory study in neuroendocrine tumors," he said.

Researchers with Yao included Marianne Pavel, M.D., Charite-Universitatsmedizin, Berlin; John Hainsworth, M.D., Cannon Research Institute, Nashville; Eric Baudin, M.D., Oncologie Endocrinienne et Medecine Nucleaire, Villejuif, France; Marc Peeters, M.D., Antwerp University Hospital, Belgium; Dieter Horsch, M.D., Klinik fur Innere Medizin, Zenttralklinik Bad Berka GmbH, Germany; Robert Winkler, M.D., Judith Klimovsky, M.D. and David Lebwohl, M.D., Ochsner Kenner Medical Center, Louisiana; Valentine Jehl, MSc, Novartis Pharma AB, Switzerland; Edward Wolin, M.D., Ceders Sinai Medical Center, Los Angeles; Kjell Oberg, M.D., University Hospital, Uppsala, Sweden; and Eric Van Cutsem, M.D., University Hospital Gasthuisberg, Leuven, Belgium. Yao is a consultant to and has received research funding from Novartis.

Laura Sussman | EurekAlert!
Further information:
http://www.mdanderson.org

More articles from Health and Medicine:

nachricht Fast-tracking T cell therapies with immune-mimicking biomaterials
16.01.2018 | Wyss Institute for Biologically Inspired Engineering at Harvard

nachricht Dengue takes low and slow approach to replication
12.01.2018 | Duke University

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: 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...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

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

Novel 3-D printing technique yields high-performance composites

16.01.2018 | Materials Sciences

New application for acoustics helps estimate marine life populations

16.01.2018 | Life Sciences

Fast-tracking T cell therapies with immune-mimicking biomaterials

16.01.2018 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>