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).
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!
NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases
Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
21.03.2018 | Physics and Astronomy
21.03.2018 | Materials Sciences
21.03.2018 | Life Sciences