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 Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Solving the efficiency of Gram-negative bacteria

22.03.2019 | Life Sciences

Bacteria bide their time when antibiotics attack

22.03.2019 | Life Sciences

Open source software helps researchers extract key insights from huge sensor datasets

22.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>