Exocrine pancreatic insufficiency and somatostatin analogs in patients with neuroendocrine neoplasia

Abstract

Gastroenteropancreatic neuroendocrine neoplasia (GEPNEN) is a heterogeneous group of rather rare cancers. Such cancers have different biological behaviors depending on both clinical and pathological features, including primary tumor site, disease staging, tumor grading, and somatostatin receptors’ expression. The presence of these receptors in GEP-NEN patients is the rationale for using the somatostatin analogs (SSAs) octreotide long-acting release (LAR) and lanreotide slow-release (autogel), which are widely recognized as first-line therapy for most GEP-NENs. In fact, in patients with slow-growing, well-differentiated, somatostatin receptor-positive tumors, which represent the most common type of GEP-NENs, both analogs have been demonstrated to be effective in controlling symptoms and inhibiting tumor growth [1,2]. These drugs are well tolerated and have an excellent safety profile. The most commonly reported side effects are abdominal pain, flatulence, diarrhea, constipation, bloating, hyperglycemia, and gallstone development [3]. Although relatively frequent, these symptoms are rarely severe, and, while treatment discontinuation is necessary for a negligible minority of patients, most of them are able to remain under treatment for long periods of time. Interpreting abdominal symptoms may be tricky in GEPNEN patients receiving SSAs owing to the possible overlap between aforementioned symptoms and carcinoid syndrome as well as previous surgery, which might result in the small bowel or pancreatic resection depending on the primary tumor site [4]. Furthermore, secretory diarrhea may be present because of short bowel, bile acid diarrhea, or bacterial overgrowth, which are also known to be potential causes for low fecal elastase levels pointing to exocrine pancreatic insufficiency (EPI) [5,6]. The onset of EPI may further confound the clinical picture in patients with NENs receiving SSAs, which may occur owing to the effects of these drugs on pancreatic function, and more specifically, inhibition of the production and secretion of pancreatic enzymes [7]. Although EPI is rarely reported in clinical trials investigating the efficacy of SSAs in GEP-NEN patients [1,2], its prevalence in daily clinical practice seems to be dramatically higher (up to 20%), as highlighted in few studies (Table 1) [7–10].