Octreotide long-acting release (LAR) in combination with other therapies for treatment of neuroendocrine neoplasia: a systematic review

Abstract

Background: In the last decades, the incidence of neuroendocrine neoplasia (NEN) increased from 1 to 5 new diagnoses/100,000 persons/year. The synthetic somatostatin analogues (SSAs) represent the first-choice treatment for both functionally active and inactive gastro-enteric-pancreatic NEN. This systematic review examines the role of octreotide long-acting release (LAR) in combination with other therapies for NEN management.Methods: Primary outcomes were the disease control rate and the progression free survival (PFS), defined as the time between treatment initiation and progression of disease. Secondary outcomes were overall survival (OS) and safety.Results: This systematic review identified 13 studies, concerning the use of octreotide LAR in association with other therapies in advanced NENs and included 1,206 patients. Patients were treated with octreotide LAR in combination with other drugs, mainly with everolimus (404 patients, 35%), but even with Peptide Receptor Radionuclide Therapy, bevacizumab, interferon or fluoride-derivatives. Disease control was observed in 85% cases with SSAs in combination with other therapies; PFS ranged from 15 to 16.4 months and OS from 25 to 61.9 months. SSAs are very well tolerated drugs, with few side effects which are usually mild, not requiring drug withdrawn. Conclusions:The review summarizes the effectiveness and available safety data on octreotide LAR in combination with other therapies in patients with NEN and may provide suggestions to address the therapeutic strategy. Further comparative head-to-head studies are needed to understand which is the best combination treatment for patients with progressive NEN after failure of first-line therapy.

Somatostatin and Its Receptor System in Colorectal Cancer

“…Clinical application of somatostatin has been limited by its very short half-life (<3 min), necessitating continuous intravenous infusion. Hence, a number of SAAs with a longer half-life (1.5–2 h) are applied in radiolabeled somatostatin analogue/peptide receptor radionuclide therapy (PRRT) [ 23 , 25 , 26 , 58 , 217 , 236 , 237 , 238 ]. Moreover, while the native SST binds to all SSTRs, OCT binds with high affinity to SST2 and SST5 [ 239 ].…”

“…Therapy with SSAs takes advantage of both the multidirectional effects of SAAs on the GI tract (e.g., reducing secretion of hormones and biologically active substances) and their antiproliferative effects to reduce tumor mass, delay disease progression, and prolong life [ 26 ]. Long-acting release (LAR) OCT has been considered a breakthrough in the treatment of all NENs for about two decades [ 244 , 245 ].…”

“…It is a suitable first-line drug or maintenance therapy and can be used in combination therapy in advanced forms of NENs, and to delay disease progression. The demonstration of the antiproliferative effect of OCT LAR has led to its approval for the treatment of patients with NENs of unknown primary location (reviewed in [ 26 ]). Another long-acting SSA is lanreotide Autogel, whose use in the CLARINET trial significantly prolonged progression-free survival (PFS) in patients with metastatic pancreatic/intestinal NETs.…”

“…Furthermore, the SRIF system is characterized by a strong antiproliferative activity, increasing cell apoptosis and inhibiting angiogenesis in most of the cancerous tissues [ 12 , 16 , 17 , 18 , 19 , 20 ]. This property is already used in clinical practice [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. SST acts through the activation of five membrane receptors (SSTRs/SSTs), belonging to the G protein-coupled receptor (GPCR) family [ 12 , 16 , 19 , 24 , 27 , 28 ].…”

The State-of-the-Art Mechanisms and Antitumor Effects of Somatostatin in Colorectal Cancer: A Review

“…SSAs treatment mainly concerns highly differentiated neuroendocrine neoplasms (NENs) of GIT and other tumors that express SSTRs. Although the importance of SSAs in the treatment of symptomatic hormonally active tumors is widely recognized, their role as anticancer drugs is controversial and still undefined [ 42 , 43 , 44 , 45 , 46 ].…”