HORMONAL TREATMENTS—SOMATOSTATIN ANALOGS (SSAS)
Biotherapy with SSAs is the mainstay of maintenance treatment for NETs. Not only are these agents effective in reducing functional symptoms, but they also retard growth in lower grade tumors. Two preparations are available, octreotide (short-acting SANDOSTATIN® and long-acting SANDOSTATIN® LAR) or lanreotide (long-acting SOMATULINE® DEPOT). The two medications have similar biological effects on the somatostatin receptors (predominantly receptor subtypes 2 and 5). Short acting SANDOSTATIN®, also known as “rescue injection,” is a water-soluble preparation given subcutaneously and lasting 4-6 hours, so it must be administered 2-4 times daily. Rescue injection is immediately bioavailable and can reduce symptoms within a few minutes. This is the option of choice for back-up for patients prone to carcinoid crisis. The longer acting formulations are particularly suited to chronic maintenance therapy and are generally well tolerated.
OCTREOTIDE (SANDOSTATIN® LAR)
has the longest history in NETs. It is formulated as a polymer that slowly releases octreotide, given as an IM injection into the gluteus muscle. It comes in doses of 10, 20, and 30 mg given every 28 days, though individual differences may require a change in 7 dosing or scheduling. The major side effects include gallstones, pain at the injection site, abdominal pain, and changes in thyroid or glucose metabolism. Subclinical fat malabsorption from pancreatic insufficiency also results after long term use of SSA. Mixing and administering the drug can be difficult. Octreotide is FDA-approved for carcinoid syndrome, VIPoma, and acromegaly. However, the PROMID Trial 2009 demonstrated that maintenance treatment also slows tumor growth.
LANREOTIDE (SOMATULINE® DEPOT)
is an aqueous nanotubule that is given as a deep sub-cutaneous injection. It is indicated for syndrome control and also is FDA-approved for tumor control with improvement in progression-free survival (PFS) (CLARINET Trial 2013). Lanreotide comes in doses of 60, 90, or 120 mg and is pre-packaged, making administration somewhat easier. Side effects are similar to octreotide.
ROLE OF SSAS IN CARCINOID CRISIS
Patients treated with octreotide LAR or lanreotide have reduced likelihood of experiencing a carcinoid crisis when undergoing invasive procedures. Intravenous infusion of octreotide is the standard treatment.
TELOTRISTAT ETHYL (XERMELO®) FOR DIARRHEA IN CARCINOID SYNDROME
is the first oral medication that can be used to control diarrhea in carcinoid syndrome (CS) by inhibiting tryptophan hydroxylase, the rate-limiting enzyme involved in the production of serotonin. It is FDA-approved for the treatment of diarrhea in patients sub-optimally treated with a somatostatin analog alone. Telotristat is not indicated for tumor control. The drug is well tolerated with minor elevations in liver enzymes. Some patients may require dose reductions because of constipation and/or abdominal pain. Telotristat does not enter the central nervous system and is not thought to be associated with depression.