Medical management of pancreatic neuroendocrine tumors.
BACKGROUND
Pancreatic neuroendocrine tumors (PNET) are rare malignancies frequently diagnosed at a late stage, with symptoms related to bulky disease. Hormonal secretion, when responsible for symptoms, permits, on the other hand, early diagnosis of the disease. Surgery remains the cornerstone of therapeutic management. However, due to advanced disease, many patients are not candidates for aggressive surgical therapy. Tumor growth control and symptom management are thus achieved through medical approaches, including somatostatin (SST) analogs, chemotherapy, interferon, and more recently, targeted therapy. The purpose of this review is to collect, examine, and analyze data available in the literature regarding contemporary therapeutic management of PNET, with emphasis on medical approaches. It also offers perspectives on the future of molecular targeted therapies in these neoplasms. However, we point out that much of the literature published to date includes noncomparative studies (mainly phase II studies), leading to thorny interpretation of the results.


METHODS
A systematic search of all the literature in English regarding PNET was performed, based on a MEDLINE search (Pubmed) carried out from January 1970 to May 2005.


RESULTS
Approximately 40 trials, including over 1,000 patients, have been retrieved from our MEDLINE search. SST analogs and interferon therapies do allow control over hormone secretion and subsequent symptoms in the majority of treated subjects, but offer a poor tumor growth control rate. Chemotherapies, although more efficient in reducing tumor burden, are often toxic. New approaches such as immunotherapy and targeted therapies are still under investigation.


CONCLUSIONS
Whether alone or in combination with surgery, conventional medical therapies represent a crucial aspect of PNET management. Hopefully, in the near future, a new era of antitumoral agents, such as targeted therapies, will strengthen our therapeutic arsenal, either alone or combined with other therapies.
Delaunoit
Thierry
T
Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Neczyporenko
Florence
F
Rubin
Joseph
J
Erlichman
Charles
C
Hobday
Timothy J
TJ
D004359:Drug Therapy, Combination; D006801:Humans; D007167:Immunotherapy; D018358:Neuroendocrine Tumors / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000628:therapy*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
D013004:Somatostatin