Medical Treatment

Some neuroendocrine tumors are so slow growing that they do not respond to conventional chemotherapy (which usually targets fast growing cells), while other neuroendocrine tumors (such as small cell carcinomas) are best treated with chemotherapy. There are several relatively new and exciting chemotherapy options available to patients with some types of neuroendocrine tumors. For example, the U.S. Food and Drug Administration (FDA) recently approved the drugs Sutent (sunitinib) and Afinitor (Everolimus) for the treatment of advanced neuroendocrine tumors. Sutent is manufactured by Pfizer, and Afinitor by Novartis. It is exciting to see that the options available for patients with neuoendocrine tumors is growing.

Afinitor was approved for the treatment of patients with progressive pancreatic neuroendocrine tumors that are not resectable surgically, that are locally advanced or metastatic. This approval by the FDA was based on a phase III clinical trial of Afinitor, in which the drug was shown to prolong progression free survival in patients with advanced pancreatic neuroendocrine tumors. This phase III trial was reported in the New England Journal of Medicine (N Engl J Med. 2011 Feb 10;364(6):514-23.). The research team at Johns Hopkins has played a role in understanding the likely mechanism by which Afinitor works. The team sequenced all of the known human genes in a series of pancreatic neuroendocrine tumors and found that one in six of these tumors harbors an activating mutation (DNA change) in the mTOR pathway. (Jiao, Shi, Edil, de Wilde, Klimstra, Maitra, Schulick, Tang, Wolfgang, Choti, Velculescu, Diaz, Jr., Vogelstein, Hruban & Papadopoulos, Science, 2011). This is the very pathway that Afinitor targets, and it is likely that Afinitor will be most effective in patients with a tumor with an mTOR pathway gene mutation.

Sunitinib belongs to the class of drugs called "tyrosine kinase inhibitors," and it has both effects against blood vessels in tumors (antiangiogenic) and effects against the tumor itself (antitumor properties). In a phase III clinical trial treatment with Sunitinib has been shown to significantly improve progression free survival in patients with metastatic pancreatic neuroendocrine tumors (PNETs) (Reviewed in: Cancer Metastasis Rev, 2011, Suppl 1:19-26).

In some instance metastases to the liver can be treated by destroying their blood supply using techniques such as hepatic artery embolization, chemoembolization or embolization using radionucleotides Radioembolization (Yttrium-90).

These approaches involve the selective cannulation of the blood vessels leading to the tumor. The vessels feeding the metastases are identified and then destroyed (embolized).

In some instances drugs can be used to block the symptoms causes by the release of hormones from the neuroendocrine tumor. For example, proton pump inhibitors can be used to counteract the high levels of stomach acid produced in patients with gastrinomas. Finally, in selected patients response rates as high as 70% have been reported following the treatment of islet cell tumors / pancreatic endocrine neoplasms with the drug streptozocin.

Clearly, there are a lot of options for the medical treatment of neuroendocrine tumors. If you would like to be seen by one of our oncologists, please contact our multi-disciplinary clinic coordinator, Suzanne Smallwood-Massey, at 877-LIVER99 (548-3799) or by e-mail: hopkinslivercenter@jhmi.edu.

PROGNOSIS

The most important prognostic factor is whether or not the tumor can be removed surgically. Other significant prognostic for patients with neuroendocrine tumor include the type of tumor, the size of the tumor, the presence or absence of blood vessel invasion, the presence or absence of metastases to lymph nodes or other organs (also known as stage), and the rate at which the tumor cells are dividing (the mitotic rate).