Using Somatostatin Analogs in pNETs

Somatostatin analogs have historically been used for symptom control in patients with pancreatic neuroendocrine tumors (pNETs); however, these agents are now being considered for their antitumor properties. Functional patients with pNETs typically receive somatostatin analogs for life, states Diane Reidy Lagunes, MD.

Somatostatin analogs are classically used for carcinoid syndrome, which typically develops in patients with small bowel metastatic disease that is typically a serotonin-secreting tumor, states Pamela L, Kunz, MD. This is measured in the urine as a 5-hydroxyindoleacetic acid (5-HIAA) level, and these patients often present with flushing and diarrhea. Kunz typically initiates patients on both a long-acting and short-acting somatostatin analog, as the long-acting medication usually takes about 2 weeks to take effect.

The phase III CLARINET study evaluated the use of the somatostatin analog lanreotide in 204 patients with well or moderately differentiated non-functioning gastroenteropancreatic neuroendocrine tumors. Participants were randomized to receive either lanreotide or placebo until disease progression or death. The progression-free survival in the placebo arm was 18 months, while the experimental arm has still not met the primary endpoint of progression-free survival at 2 years. This indicates that patients on lanreotide have still not progressed on a well-tolerated medication, notes Lagunes, demonstrating the association of cytostatic control with somatostatin analogs.

There is a dramatic improvement once somatostatin analog therapy is begun in VIPomas, a type of pNET that secretes vasoactive intestinal peptide (VIP), says Lagunes. For other types of neuroendocrine tumors, such as gastrinoma, a proton pump inhibitor may be sufficient in controlling symptoms.

Carcinoid crisis is a hemodynamic instability caused by a massive release of hormones in the systemic circulation that overwhelms the patient’s ability to cope, explains Rodney Pommier, MD. Crisis can occur in patients with functional and nonfunctional pNETs. Two very well known triggers for carcinoid crisis are anesthesia and surgery, making it important to monitor for crisis in individuals with carcinoid syndrome.

Risk factors for carcinoid crisis include the presence of carcinoid syndrome, female gender, age, and length of operation. Carcinoid crisis occurs almost exclusively in patients with liver metastases, adds Pommier. The administration of the somatostatin analog octreotide before or during an operation has been shown to prevent a crisis.