Treatment Option Overview
If technically and medically feasible, primary management of endocrine tumors of the pancreas involves surgical resection with curative intent. Given the rare nature of these tumors, surgical approaches are based upon case series and expert opinion rather than randomized controlled trials. The surgical options listed below are based on retrospective series from single reporting centers.[2-4][Level of evidence: 3iiD or 3iiiD]
Adjuvant therapy has no proven benefit and is, therefore, investigational. There have been no well-controlled trials of adjuvant therapy after complete tumor resection.Surgical Cytoreduction for Metastases
Surgery plays a role even in the setting of metastatic disease. The symptoms of metastatic functional pancreatic neuroendocrine tumors (NETs) may be ameliorated by the reduction of overall tumor burden through surgical debulking.
The liver is a common site of metastasis from pancreatic NETs. Because of the slow growth rate of many NETs, liver metastases are often resected when technically feasible. Resection of all grossly visible liver metastases can be associated with long-term survival and, in the case of symptomatic hormonally functional tumors, symptom relief. Most symptoms from functional tumors respond to this form of surgical debulking. How much of the favorable survival rates is attributable to patient selection factors is not known (e.g., underlying patient condition, extent of metastases, slow doubling time, and so forth).
A variety of alternative approaches to the management of liver metastases have been reported, including gel-foam embolization or transarterial chemoembolization, radioembolization with radioactive microspheres,[8-10] radiofrequency ablation, cryoablation, and percutaneous alcohol ablation. These alternative approaches have been reviewed.
Results from surgical resection series appear to be more favorable than with these techniques, and surgery is considered to be the standard approach to resectable liver metastases. However, there are no high-quality studies comparing the various approaches. A systematic review of evidence comparing liver resection versus other treatments for patients with resectable liver neuroendocrine metastases found no randomized trials, or even quasi-experimental, cohort, or case-control studies in which the patient population given the alternative therapies was similar enough to the surgery group to draw reliable conclusions. The evidence for resection of all grossly visible liver metastases derives solely from case series.[Level of evidence: 3iiD or 3iiiD]
In most cases, liver metastases are not completely resectable. Cytoreductive surgery, with or without radiofrequency ablation or cryoablation, has been used to palliate symptoms. A systematic review found no randomized or quasi-randomized trials comparing cytoreductive surgery to other palliative approaches such as chemotherapy or tumor product inhibitors. The evidence for surgical cytoreduction of unresectable liver metastases is restricted to case series [Level of evidence: 3iiD or 3iiiD], and interpretation of outcomes may be strongly affected by patient selection factors.Systemic Therapy for Advanced and Metastatic Disease
Somatostatin analogs may be effective in reducing the symptoms of functional tumors.
Chemotherapy using drugs such as the following, either alone or in combination, has been shown to have antitumor effects, but evidence is weak or conflicting regarding the impact of chemotherapy on overall survival:[15-17]
- Tyrosine kinase inhibitors (e.g., sunitinib).
- Vascular endothelial growth factor pathway inhibitors.
- Mammalian target of rapamycin inhibitors (e.g., everolimus).
Nearly all of the evidence of activity derives from case series.[Level of evidence 3iiiDiv] However, there are ongoing placebo-controlled randomized trials of everolimus  and sunitinib  that have been reported in abstract form showing an increase in progression-free survival in each case.[Level of evidence 1iDiii]
Favorable responses have been reported in patients with advanced progressive pancreatic NETs after treatment with several radiolabeled somatostatin analogs in which the analogs octreotide, octreotate, lanreotide, or edotreotide are stably attached to the radionuclides 111Indium, 90Ytrium, or 177Lutrium.[21-23] The relative efficacy of these various compounds is unknown. Study designs have been limited to case series with tumor response, biochemical response, or symptom control as the measure of efficacy.[Level of evidence 3iiiDiv]
As noted in each of the clinical situations, there is a paucity or absence of high-level evidence, and a need for randomized controlled trials.Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with islet cell carcinoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
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- Kazanjian KK, Reber HA, Hines OJ: Resection of pancreatic neuroendocrine tumors: results of 70 cases. Arch Surg 141 (8): 765-9; discussion 769-70, 2006. [PUBMED Abstract]
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- Yao JC, Shah MH, Ito T, et al.: A randomized, double-blind, placebo-controlled multicenter phase III trial of everolimus in patients with advanced pancreatic neuroendocrine tumors (PNET) (RADIANT-3). [Abstract] Ann Oncol 21 (Suppl 8): A-LBA9, viii4-5, 2010.
- Raymond E, Niccoli-Sire P, Bang Y: Updated results of the phase III trial of sunitinib (SU) versus placebo (PBO) for treatment of advanced pancreatic neuroendocrine tumors (NET). [Abstract] American Society of Clinical Oncology 2010 Gastrointestinal Cancers Symposium, 22–24 January 2010, Orlando, Florida. A-127, 2010.
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