Somatostatin Analogues for the Treatment of NETs

Transcript:

Andrew E. Hendifar, MD: Somatostatin analogue therapy is the cornerstone of treatment of neuroendocrine tumors that express the somatostatin receptor, as well as the most important component of treatment for carcinoid syndrome. Somatostatin analogue therapies have been used for decades to help control the syndrome by reducing diarrhea and reducing flushing, as well as to help control progression-free survival in patients. They were originally conceptualized for midgut neuroendocrine tumors. More recently, their use has been expanded to all neuroendocrine tumors that are well differentiated and expressed to the somatostatin receptor.

Eric Liu, MD, FACS: Somatostatin analogues have been a truly revolutionary invention in medicine; maybe second only to insulin, which may be the most important hormone that we’ve created. It’s helped many patients, and it’s been around for 30 years. People don’t realize it’s helped so many patients.

But there are actually different ways that it helps people. Originally, when it came out, it was just to help with the symptoms. It was designed to help with the carcinoid syndrome—the diarrhea and those kinds of things. But actually, recently we’ve discovered that even this synthetic hormone that we give can have an effect on tumor growth. So now you get 2 for 1. You get symptom control, which helps with the quality of life, and hopefully tumor control, which helps with the quantity of life.

The somatostatin analogue has been the absolute foundation for the treatment for all neuroendocrine tumors. Hopefully more and more patients can get it, so they can have a better quality and quantity of life.

A somatostatin analogue is actually a small synthetic hormone that’s a copy of 1 that we all make, called somatostatin. What it does is it binds to receptors inside your body, which help to slow down multiple bodily functions—digestion, hormone production, and those kinds of things.

It’s great as a normal hormone in your body, but remember, it has a half-life of only 2 minutes. This means it goes away very fast. This is important for your body because you can always make more hormone, and you can destroy it. So you can control it. It’s like an on-off switch.

But that means the hormone doesn’t work very well as a medicine. In the 1980s, the medicine that was created was called octreotide, which was a shortened version of somatostatin. It was a formulation that really changed the lives of many of our neuroendocrine patients. It originally came out to help with symptom control, including diarrhea and flushing. Unfortunately, when it first came out, it came out like an injection, almost like insulin. It lasted for only 4 to 6 hours, and you had to give yourself multiple shots per day. Now, that’s certainly better than having 20 bouts of diarrhea per day. So it was very important for helping patients.

But then later in the 1980s and early 1990s, a new formulation came out. This was a long-acting version that could be given once a month. This long-acting repeatable version of octreotide, called Sandostatin, could now be given as once-a-month therapy to help with the patient’s symptoms.

We’ve been using that formulation for 20 years. However, about 4 years ago a new medicine called lanreotide came out, or Somatuline. This medication is a slightly different formulation. It’s still a somatostatin analogue. It still does very similar biologic things. The difference was how it was created. Lanreotide is actually a crystal of the somatostatin analogue. Unlike the octreotide version, which comes as a version that kind of mixes with what we call excipients—chemicals that help to slow down the release of the molecule—lanreotide is nothing more than water and lanreotide, which is just a crystal. And when the injection is given, it slowly dissolves into the patient’s body and is absorbed, and you can get the effects of a somatostatin analogue. We’re very blessed to have multiple formulations of somatostatin analogues to help our patients.

The optimal time to introduce a somatostatin analogue to the treatment regimen actually depends on the patient. There are, as always, many variables to consider before starting treatment. One is you want to know, is their disease very fast? Do they have a lot of disease? Maybe you can observe it for a little while before you start treatment.

However, in general, a lot of patients have symptoms as well. You want to provide that relief of their symptoms as soon as possible. You don’t want the patient to suffer, obviously. If you feel someone is symptomatic, definitely, it’s a good time to start a somatostatin analogue.

However, it’s a bit more controversial if the patient is asymptomatic. We want to use it to control their tumors. It’s been demonstrated through clinical trials that somatostatin analogues can slow down tumor growth. Therefore, if someone begins to progress, that would be the time that you would start the somatostatin analogue.

Transcript Edited for Clarity