Endocrine tumors of the gastrointestinal tract: systemic treatment.

Neuroendocrlne gut and pancreatic tumors are neoplasms that present distinct features from other malignant tumors. Firstly, In most patients, tumor growth Is rather slow, and even In advanced metastatlc disease, there Is very little Impairment of the general well-being of the Individual, e.g. appetite and weight. Secondly, these tumors are known to produce specific peptlde hormones which may be factors In some clinical conditions e.g. carclnold, Zolllnger-Ellison and hypoglycemlc syndromes. These conditions can be critical to the patients and can occasionally be lethal. Therefore, the treatment of neuroendocrlne tumors must control the clinical symptoms related to hormone over-production and prevent further tumor growth. These two features are not always In parallel. Systemic treatment of neuroendocrlne tumors mainly consists of chemotherapy, Interferon and somatostatln analog administration. Chemotherapy has been used for at least 30 years; the most effective combination has proved to be streptozotocln with 5-fluorouracll or adrlamycln. This combination produces biochemical responses In up to 60% of patients with endocrine pancreatic tumors; the results In carclnold patients are very poor and response rates are ≤0%. Alpha-lnterferon (IFNa) produces biochemical responses In approximately 50% of patients with malignant carclnoid tumors, significant reductions In tumor size In 15% and a further 39% of patients have disease stabilization with no further tumor growth. Somatostatln analogs have only been used clinically within the last 10 years, but produce symptomatic Improvement in 70% of cases, biochemical responses In 40-60%, but rarely produce any significant reduction In tumor size. These analogs are particularly useful to control severe clinical symptoms and are the first-line therapy for the management of carclnold patients both perland intra-operatlvely. Patients with endocrine pancreatic tumors, particularly those with glucagon and vasolntest- Inal peptlde-produclng tumors, benefit most from this type of treatment. Recently, a combination of IFN-a and a somatostatln analog has showed an additive effect of these two drugs. The side effects of streptozotocln and 5- fluorouracil are mainly nausea and vomiting which can be controlled with 5-HT3 receptor blocker therapy. Another significant adverse reaction Is impaired renal function. The adverse reactions to IFN-a are mainly flu-like symptoms, fatigue, mild Impairment of liver and bone marrow function and autoimmune reactions In 15% cases. Somatostatln analog treatment causes a low frequency of adverse reactions, those which do occur Include gall stone formation and steatorrhea. Future systemic treatment should be based on increased knowledge of the tumor biology, particularly growth-regulatory mechanisms. At present, the majority of treatment Is to control the disease. Therapies to cure patients with advanced stages of neuroendocrlne tumors have yet to be established.