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.

Fig. 1

Treatment algorithm of advanced NENs. AC, atypical carcinoid; CAPTEM, capecitabine-temozolomide; CDDP, cisplatin; CBCDA, carboplatin; CT, chemotherapy; EVE, everolimus; FOLFIRI, 5-fluorouracil and irinotecan; FOLFOX, 5-fluorouracil and oxaliplatin; INF, interferon-alfa; NENs, neuroendocrine neoplasias; NET, neuroendocrine tumor; NEC, neuroendocrine carcinoma; PRRT, peptide receptor radionucleotide therapy; SSA, somatostatine analogues; STZ-5FU, streptozocin-5 Fluorouracile; SUN, sunitinib;TC, typical carcinoid; VP-16, etoposide. ^aIn somatostatin-receptor imaging positive tumors and/or refractory hormonal síndrome. ^bChemotherapy preferred upfront over targeted agents in G3 NETs. ^cWatch and wait may be considered in G1 very indolent tumors, particularly in older or frail patients. ^dCAPTEM may be considered after progression to all available treatments in selected patients with good PS and rapidly progressing tumors. ^eChemotherapy may be considered upfront in selected patients (rapidly progressing tumors, Ki-67>20%).^fEnrollement in clinical trials is recommended if available.^gCarboplatin is preferred over cisplatin due to its more favorable toxicity profile.^hThe treatment choice should be based on response to prior therapy, toxicity profile, residual toxicity from prior chemotherapy (i.e. neurotoxicity) and patient’s comorbidities and preferences (i.e. oral vs iv)