Practice Pearl 2: Indications and Safety Data of the Somatostatin Analogues for NETs


The panel of experts in the management of NETs review the indications and safety data of the somatostatin analogues.

Megan May, PharmD, BCOP: What are the indications in each of these? Octreotide has 3 main indications related to neuroendocrine tumors. It is indicated for symptomatic metastatic carcinoid syndrome. It is also indicated in neuroendocrine tumors and for diarrhea that is associated with vasoactive intestinal peptide-secreting tumors. Lanreotide has 2 indications related. It is indicated for carcinoid syndrome and also in GI [gastrointestinal] and pancreatic neuroendocrine tumors.

Daneng Li, MD: I completely agree. It is always hard to compare across trials. In terms of the octreotide study, the PROMID study was predominantly only patients with neuroendocrine-MICA tumors, and the lanreotide treatment involved gastroenteropancreatic neuroendocrine tumors. The open-label extension data are very intriguing, but at the same time, we have to make a caveat: It is only part of an exploratory analysis. It is potentially hypothesis generating, since we get a clue of possibly what the PFS [progression-free survival] is. Certainly, that was not the primary end point of the study, however. We do have to caution the audience regarding that.

For the most part, they are very similar in terms of the characteristics that you mention, like potential tumor suppression as well as hormonal suppression. Lanreotide, obviously, with the CLARINET study specifically, was done for antitumor activity, whereas the original octreotide studies were conducted for carcinoid syndrome. Where you get the data for potential antitumor activity is with the PROMID study, which you mentioned for MICA-neuroendocrine tumors.

Have you noticed, Cecilia, any differences in safety or potential drug interactions with these 2 somatostatin analogues [SSAs]?

Cecilia Lau, RPh, BCOP, APh: In terms of safety and drug interactions, these drugs are fairly similar. One of the more prevalent adverse effects is actually the occurrence of gallstones, which can happen in up to 50% of patients. Prophylactic cholecystectomy is often recommended. If the patient is to undergo surgery for other reasons, then a prophylactic cholecystectomy is recommended at the same time.

The other adverse effects of particular interest, especially in terms of drug interactions, is that those somatostatin analogues can cause either hypoglycemia or hyperglycemia. Obviously this has implications for patients, particularly for diabetic patients who are undergoing treatment with antidiabetes medications. They need to be more closely monitored. Additionally, the somatostatin analogues can cause bradycardia in patients with cardiac conditions. This may necessitate the use of bradycardic drugs such as beta-blockers, calcium channel blockers, digoxin. They also need to be more closely monitored. Then the SSAs can also decrease the clearance of cytochrome P450 and 3A4 substrates because of the suppression of growth hormones. The use of any 3A4 substrates that have a low therapeutic index should be used with caution, or the patients need to be closely monitored as well.

Daneng Li, MD: Those are all really good pearls to keep in mind, especially because many of these patients might be on different types of medications, as you’ve highlighted. It is really good to know that, even for a relatively benign treatment, there are still some considerations when we are prescribing these medications to keep in mind for these patients.

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