Systemic therapy in unresectable or metastatic NETs

principles of systemic therapy in patients with unresectable or metastatic NETs?

There is no known role for adjuvant systemic therapy. Patients who have metastatic NETs and carcinoid syndrome should be treated with a somatostatin analogue (octreotide or lanreotide). The long-acting release (LAR) preparations are often effective for symptom management; intercurrent symptom flares can be treated by temporarily adding a short-acting somatostatin analogue. Telotristat is orally administered for the inhibition of tryptophan hydroxylase, which is the rate-limiting step in serotonin synthesis. Telotristat can be used in combination with somatostatin analogues and has been shown to significantly reduce both 5-HIAA excretion and diarrhea. There is no consensus on initiation of treatment in the asymptomatic patient with a low tumor burden. The use of octreotide or lanreotide in patients with clinically significant tumor burdens or progressive disease can help control tumor growth. Systemic chemotherapy and hepatic artery embolization have not been very effective in palliative therapy for patients with diffuse hepatic metastases; however, selective hepatic artery chemoembolization, when possible, has been successful in decreasing tumor burden and alleviating symptoms.

For patients with progressive metastatic carcinoid, everolimus (an inhibitor of mechanistic target of rapamycin) can be given with octreotide LAR. Cytotoxic chemotherapy regimens, such as combination capecitabine and oxaplatin, or 5-fluorouracil, streptozotocin, or doxorubicin, have shown only modest response rates. Patients who have failed to respond to somatostatin analogues can be treated with interferon-alpha. There are some reports of benefit from treatment with radiolabeled somatostatin analogues in patients with advanced disease.

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