The safety of available treatments options for neuroendocrine tumors

Abstract

Neuroendocrine neoplasms (NEN) represent a heterogeneous group of malignancies generally characterized by low proliferation and indolent course. However, about half of the newly diagnosed cases are metastatic and require long-term systemic therapies. Areas covered: This review revises the literature to summarize the current knowledge upon safety of all systemic treatment options available. Thirty three different clinical studies have been considered, including 4 on somatostatin analogues (SSA), 5 on targeted therapies, 10 on peptide receptor radionuclide therapy (PRRT), and 14 on chemotherapy. Expert opinion: SSA are safe and well tolerated without any relevant severe adverse event and very low treatment discontinuation rate. Targeted therapies show a satisfying safety profile. Most adverse events are grade 1-2 and easy manageable with dose reduction or temporary interruption. PRRT is manageable and safe with a low rate of grade 3-4 adverse events. However, severe renal and hematologic toxicity may occur. Chemotherapy is usually considered after previous therapeutic lines. Therefore, these subjects are more susceptible to experience adverse events due to cumulative toxicities or poor performance status. The available systemic treatment options are generally well tolerated and suitable for long-term administration. Cumulative toxicity should be taken in account for the definition of therapeutic sequence.

Somatostatin Analogs in Clinical Practice: A Review

“…Alopecia has also been reported [191]. High doses of SSAs have not shown differences in common adverse events when compared to standard doses [192].…”

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

“…Concerning medical therapy of GEP-NET, SSAs are the treatment of choice in patients with low grade G1-G2 tumor, in functional syndrome, if surgical resection cannot be performed or in case of metastatic disease [12]. The most common SSA side effects are steatorrhea, flatulence, nausea, and abdominal pain, all induced by inhibition of pancreatic digestive enzymes secretion and suppression of intestinal motility, regardless of dosage or formulation (octreotide or lanreotide) used [71]. SSAs may reduce intestinal fluid secretion and also the secretion of pancreatic enzymes and bile acids, which diminish fat absorption.…”

“…A study in an osteotropic breast cancer model demonstrated that everolimus had a bone-protective efficacy both in vitro and in vivo, by impairing osteoclastogenesis and preventing the bone loss [74]. Moreover, everolimus has been associated with nausea, vomiting anorexia, stomatitis, and diarrhea-all factors indicating a malnourished status [71]. Sunitinib is an oral multitarget tyrosine kinases inhibitor (TKI), which mainly binds the vascular endothelial growth factor (VEGF) receptors and the platelet-derived growth factor (PDGF) receptors.…”

“…However, it has been associated with an increased risk of osteonecrosis of the jaw in patients with bone metastatic renal cell carcinoma who were treated with bisphosphonates [75]. Sunitinib is also associated with diarrhea and possible other complications related to malnutrition and vitamin D malabsorption [71]. Cabozantinib is a new TKI that is currently under investigation in metastatic pNET.…”

Therapeutic sequences in patients with grade 1−2 neuroendocrine tumors (NET): an observational multicenter study from the ELIOS group

“…Whereas the treatment of choice of localized NET is surgical resection, a wide spectrum of therapeutic options is available for patients with advanced, unresectable NET. The management of patients with metastatic or regionally advanced G1 or G2 gastroenteropancreatic (GEP) and lung NET is based on different therapeutic options such as somatostatin analogs (SSA), molecular targeting therapies (everolimus and sunitinib), chemotherapy and peptide receptor radionuclide therapy (PRRT) [3][4][5]. These can be used alone or as a multimodal approach.…”