Advances in the treatment of neuroendocrine tumors

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Abstract
Gastrointestinal neuroendocrine tumors are characterized by generally slow growth rates and the ability to secrete a variety of hormones and biogenic amines. For patients with localized disease, surgical resection alone is often curative; however, patients with metastatic disease often present a therapeutic challenge. Although somatostatin analogs are highly effective in controlling symptoms of hormonal secretion, they are rarely associated with tumor regression. Selected patients with hepatic metastases may benefit from surgical debulking, embolization, or other ablative therapies. The clinical benefit associated with the administration of systemic agents such as alpha interferon or cytotoxic chemotherapy is less clear, and the widespread use of such regimens has been limited by their relatively modest antitumor activity as well as by concerns regarding their potential toxicity. The highly vascular nature of neuroendocrine tumors has led to interest in angiogenesis inhibition as a potentially novel treatment strategy. In addition, several small molecule tyrosine kinase inhibitors are currently being evaluated in a Phase II setting. The naturally indolent growth of neuroendocrine tumors presents a challenge in interpreting efficacy endpoints from small Phase II studies. Larger, randomized trials, along with the evaluation of surrogate endpoints of biologic activity, may be necessary to establish the potential clinical benefit of these novel agents.