Signaling mechanisms in neuroendocrine tumors as targets for therapy.
Endocrinol Metab Clin North Am. 2010 Dec;39(4):801-10
Authors: Zarebczan B, Chen H
Although neuroendocrine tumors are rare, the more common types such as gastrointestinal and pancreatic carcinoids, medullary thyroid cancers, and small cell lung cancers have been studied in detail during the last few years. Data published thus far indicate that multiple signaling pathways are involved in these cancers. Recent focus has been on developing novel therapeutics by targeting specific signaling pathways. This article details several of the signaling mechanisms that have been discovered to play a role in the development and progression of neuroendocrine tumors. The therapeutic options developed to address the various pathways, including their specific mechanisms of actions, are also discussed.
In two separate Phase III clinical trials, the targeted drugs Sutent® (sunitinib) and Afinitor® (everolimus) delayed the progression of advanced pancreatic neuroendocrine tumors. These results were published in the New England Journal of Medicine.
Pancreatic neuroendocrine tumors are a relatively uncommon type of cancer that develops in the hormone-producing cells of the pancreas.
Sutent is an oral targeted agent that works by inhibiting multiple biologic pathways involved in the growth, replication, and spread of cancer cells. It has been shown to be effective in the treatment of selected patients with kidney cancer or gastrointestinal stromal tumors, and is also being evaluated in the treatment of other types of cancer.
To evaluate Sutent for the treatment of advanced pancreatic neuroendocrine tumors, researchers conducted a Phase III clinical trial among 171 patients who had experienced cancer progression. Half the patients were treated with Sutent, and half were treated with a placebo.
Progression-free survival was 11.4 months among patients treated with Sutent and 5.5 months among patients treated with placebo.
Patients treated with Sutent also experienced better overall survival than patients treated with placebo.
The most common serious side effect of Sutent was neutropenia (a low white blood cell count), which affected 12% of patients.
A second clinical trial evaluated Afinitor for the treatment of advanced pancreatic neuroendocrine tumors. Afinitor is an oral targeted therapy that works by inhibiting a protein known as the mammalian target of rapamycin (mTOR). The mTOR protein plays an important role in regulating cancer cell division and blood vessel growth. Afinitor is used in the treatment of selected patients with kidney cancer or subependymal giant cell astrocytoma (SEGA), and is also being evaluated for the treatment of other types of cancer.
The study of Afinitor enrolled 410 patients with advanced, low-grade or intermediate-grade pancreatic neuroendocrine tumors. Half the patients were treated with Afinitor and half were treated with a placebo.
Progression-free survival was 11 months among patients treated with Afinitor and 4.6 months among patients treated with placebo.
34% of patients treated with Afinitor were alive and free of cancer progression at 18 months, compared with 9% of patients treated with placebo.
Serious side effects of Afinitor included anemia and high blood sugar.
The results of these studies suggest that Sutent and Afinitor may improve outcomes among patients with advanced pancreatic neuroendocrine tumors.
References:
Raymond E, Dahan L, Raoul J-L et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364:501-513.
Yao JC, Shah MH, Ito T et al. Everolimus for advanced pancreatic neuroendocrine tumors. New England Journal of Medicine. 2011;364:514-523. news.cancerconnect.com
In two separate Phase III clinical trials, the targeted drugs Sutent® (sunitinib) and Afinitor® (everolimus) delayed the progression of advanced pancreatic neuroendocrine tumors. These results were published in the New England Journal of Medicine.
Pancreatic neuroendocrine tumors are a relatively uncommon type of cancer that develops in the hormone-producing cells of news.cancerconnect.com
According to an article in WebMD¸”two kidney cancer drugs show promise for the treatment of the rare type of pancreatic cancer that Apple CEO Steve Jobs was diagnosed with in 2004.” The studies were published in last week’s edition of the New England Journal of Medicine, where the researchers reported that targeted therapies dramatically improved disease-free survival times in patients with pancreatic neuroendocrine tumors. One drug was Pfizer’s Sutent, and the other was Afinitor from Novartis. David C. Metz, MD, co-director of the Neuroendocrine Tumor Program and associate chief of Gastroenterology for Clinical Affairs, is quoted throughout the article. “For the first time in 20 years we have a whole new group of drugs to treat this disease,” said Dr. Metz. “The questions are, which drug do we use first and do we combine them. We don’t have the answers yet.” www.webmd.com
...Read On
You can link to this article on your web site using following code:
Website Code:
Forum Code:
Comments
We're looking for comments that are interesting, substantial or highly amusing. If your comments are excessively self-promotional (use your real name, no keywords please), obnoxious, or even worse, boring, you will be banned from commenting. Your comment must be related to the post. Please do not comment on how great or wonderful the post is. All comments are moderated and, if approved, will display in less than 24 hours.
