Chemotherapy in NEN: still has a role?

Abstract

Neuroendocrine neoplasms (NENs) comprise a broad spectrum of tumors with widely variable biological and clinical behavior. Primary tumor site, extent of disease, tumor differentiation and expression of so matostatin receptors, proliferation and growth rates are the major prognostic factors that determine the therapeutic strategy. Treatment options for advanced disease have considerably expanded in recent years, particularly for well differentiated tumors (NETs). Novel drugs approved over the past decade in this context include somatostatin analogues and 177Lu-oxodotreotide for somatostatin-receptor-positive gastroenteropancreatic (GEP) NETs, sunitinib for pancreatic NETs (P-NETs), and everolimus for P-NETs and non-functioning lung or gastrointestinal NETs. Nevertheless, chemotherapy remains an essential component of the treatment armamentarium of patients with NENs, particularly of patients with P-NETs or those with bulky, symptomatic or rapidly progressive tumors (generally G3 or high-G2 NENs). In this manuscript we will comprehensively review available evidence related to the use of chemotherapy in lung and GEP NENs and will critically discuss its role in the treatment algorithm of this family of neoplasms.

Temozolomide in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Multicenter Retrospective Review

“…16 In addition, there has been some conjecture as to a differential response to CAPTEM and platinum doublet regimens according to differentiation status. Specifically, some experts think that poorlydifferentiated NECs may respond better to cisplatin/ etoposide, whereas WDNENS may respond better to CAP-TEM 35 . Whilst the response rate was numerically higher in patients with Ki-67<55% and in WDNENs in our cohort, the difference was not statistically significant.…”

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

“…There has been no prospective, randomized controlled study investigating the efficacy of PRRT in panNENs only, although its high anti-tumor activity was reported from a retrospective database involving many panNEN patients [ 59 ], as well as in other non-prospective studies [ 37 , 38 , 55 ]. Most studies reporting the efficacy of chemotherapies and liver-directed therapies were performed more than a decade ago in the form of single-arm, non-randomized, retrospective studies in a small cohort of patients, and thus their exact roles in the treatment sequence including various recently-developed therapeutic options remain uncertain [ 108 ]. In panNEN patients with G3 NEC (poorly-differentiated) tumors, platinum-based chemotherapy, primarily the combination of cisplatin and etoposide, is recommended as first-line therapy, whereas possible options for second-line treatment include temozolomide-, irinotecan- or oxaliplatin-based regimens [ 66 , 67 ].…”

Personalized functional profiling using ex-vivo patient-derived spheroids points out the potential of an antiangiogenic treatment in a patient with a metastatic lung atypical carcinoid

“… 2 The incidence of lung and gastroenteropancreatic (GEP) neuroendocrine tumors (NET) has significantly risen over the last 40 years, likely due to improved diagnosis. 3 …”

“…The treatment of GEP-NET has achieved considerable advances in the last decades with the introduction of sunitinib, everolimus, somatostatin analogs and peptide receptor radionuclide therapy (PRRT) (for somatostatin receptor-positive GEP-NET) in the therapeutic scheme. 3 , 4 However, everolimus is still the only treatment approved by the US Food and Drug Administration (FDA) for patients with lung NET, in particular those suffering from advanced, progressive, nonfunctional pulmonary NET, highlighting the need for more treatment options in this indication. 1 , 3 , 5 , 6 …”

“… 3 , 4 However, everolimus is still the only treatment approved by the US Food and Drug Administration (FDA) for patients with lung NET, in particular those suffering from advanced, progressive, nonfunctional pulmonary NET, highlighting the need for more treatment options in this indication. 1 , 3 , 5 , 6 …”