title: Treatment Strategies for Metastatic Neuroendocrine Tumors of the Gastrointestinal Tract.
abstract: The therapeutic landscape of gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) has evolved significantly in recent years. Current and emerging treatment options include somatostatin analogs, radiolabeled somatostatin analogs, the mTOR inhibitor everolimus, and the tyrosine kinase inhibitor sunitinib. Although high-quality data from phase III trials are lacking, cytotoxic agents are commonly used for the treatment of poorly differentiated neuroendocrine carcinomas and well-differentiated NETs originating in the pancreas. Hepatic-directed therapies are recommended for patients with slow-growing, liver-predominant disease but have never been compared to systemic agents. Telotristat ethyl, a novel serotonin synthesis inhibitor, has recently demonstrated efficacy in palliating diarrhea in patients with poorly controlled carcinoid syndrome. In the absence of definite predictive biomarkers, therapeutic decisions in most cases rely on clinical and pathological criteria. However, navigating the current therapeutic algorithm may be challenging, and future trials need to address several important questions: what is the best sequence of treatment? Is there a role for combination therapies in GEP-NETs? Are neoadjuvant, adjuvant, or maintenance strategies safe and effective? Do all NET patients require active treatment? What new molecular targets can be clinically exploited? A tight integration between basic and clinical research is needed to further advance the field of NETs.
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Cives
authors.affiliation: Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA. jonathan.strosberg@moffitt.org.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Strosberg
mesh_terms: D000465:Algorithms; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D000066491:Clinical Decision-Making; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D005770:Gastrointestinal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D006801:Humans; D007414:Intestinal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000473:pathology* / Q000628:therapy*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: CLARINET; Carcinoid tumors; NETTER-1; RADIANT-4; TELESTAR