Management of Neuroendocrine Tumors: Current and Future Therapies

Kjell E Öberg

Disclosures

Expert Rev Endocrinol Metab. 2011;6(1):49-62. 

In This Article

Symptomatic & Biochemical Control

Octreotide

Initial evidence demonstrating that octreotide can reduce symptoms of carcinoid syndrome and decrease 5-HIAA levels was shown with the subcutaneous formulation.[37,38] Currently, the long-acting repeatable (LAR) formulation, which is administered monthly (20–30 mg/month) thus eliminating the need for daily injections, is the mainstay of treatment for carcinoid syndrome. The first controlled study of octreotide LAR for treating carcinoid syndrome was conducted in 93 patients with NETs over at least 20 weeks.[24] There was a significant decrease in the number of daily stools (42%) and an 84% reduction in the incidence of flushing (0.7–4.5 episodes/day). Treatment success was achieved in 66% of patients receiving octreotide LAR 10–30 mg/month. Octreotide LAR also decreased 5-HIAA levels by 50%.[24] This study demonstrated that monthly octreotide LAR was at least as effective as subcutaneous octreotide for symptom control. The efficacy of octreotide LAR for symptomatic and biochemical control in NETs have subsequently been demonstrated in a number of studies.[39,40] The mechanism by which somatostatin analogues normalize bowel function is not yet clear, however, it is thought to involve inhibition of gut hormone secretion,[41,42] lengthening of intestinal transit time,[43] increased water and electrolyte absorption[24,44] and reduced splanchnic blood flow.[43] Treatment with octreotide can also improve survival in patients with carcinoid crisis;[45] prophylactic use is mandatory to prevent the development of a crisis. Octreotide is generally well tolerated during the treatment of carcinoid syndrome;[24] these findings have been confirmed during long-term (3-year) treatment.[39] The most common side effects, such as abdominal discomfort and bloating, are generally mild and resolve spontaneously within the first week. Gallstones can develop, although only a small proportion of patients develop clinical symptoms. Local pain at the injection site has also been reported.

Lanreotide

Lanreotide is less widely studied than octreotide for symptomatic and biochemical control and no directly comparative trials have been conducted. The sustained release formulation (Somatolin Autogel®, Ipsen), which is administered every 28 days, has shown improvement in symptom control.[31] The effects of lanreotide on symptom relief are comparable with those of octreotide.[31] One study of 71 patients who received Somatuline for 6 months found that 65% achieved a 50% or greater reduction in flushing episodes, and 18% had a 50% or greater reduction in diarrhea episodes.[46] The biochemical response rate observed with lanreotide is also comparable to that of octreotide,[31,47] with response being greater in patients naive to somatostatin analogue therapy.[46]

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