TY - JOUR
T1 - Biological targeted therapies in patients with advanced enteropancreatic neuroendocrine carcinomas
AU - Fazio, Nicola
AU - Cinieri, Saverio
AU - Lorizzo, Katia
AU - Squadroni, Michela
AU - Orlando, Laura
AU - Spada, Francesca
AU - Maiello, Evaristo
AU - Bodei, Lisa
AU - Paganelli, Giovanni
AU - Delle Fave, Gianfranco
AU - De Braud, Filippo
PY - 2010/11
Y1 - 2010/11
N2 - Enteropancreatic (EP) neuroendocrine carcinomas (NECs) represent relatively rare and heterogeneous malignancies. They are the most common group among neuroendocrine tumors (NETs). In most cases they are advanced at diagnosis and slow-growing, therefore conditioning a better prognosis compared with non neuroendocrine carcinomas from the same sites. No standard medical therapy exists, except for somatostatin analogs in functioning tumors, and octreotide LAR in functioning or non functioning well differentiated NECs from small bowel. Several systemic therapeutic options exist, including chemotherapy, somatostatin analog, interferon, peptide receptor radionuclide therapy (PRRT), and molecular targeted drugs. Among them some therapies have specific biological tumor targets and can be defined as " biological targeted therapies" This review focuses on the status of EP NECs targeted therapies in the light of recent advances. Somatostatin receptors (SSTRs) are the first therapeutic target detected in EP NECs. Through them SS analogs and PRRT act, producing symptomatic, biochemical, and, to a lesser extent, antiproliferative effects. New SS analogs, covering a higher number of SSTR subtypes, were developed, including pasireotide (SOM230), which controls 25% of carcinoid syndromes resistant to full dose octreotide LAR. Chimeric analogs, which bind SSTR2/SSTR5 and dopamine-2 receptor subtype (D2), are in preclinical phase of development. Among the numerous molecular targeted agents investigated in NETs, mTOR inhibitors and VEGF/VEGFR/PDGFR inhibitors are in most advanced clinical phase of investigation. In particular, everolimus, sunitinib, and bevacizumab are all studied in phase III trials. Both everolimus and sunitinib produced significant survival benefit versus placebo in advanced progressing well-differentiated pancreatic NECs. Sunitinib data have been presented at the last ASCO in June 2010, and everolimus data will be presented at next ESMO in September 2010.
AB - Enteropancreatic (EP) neuroendocrine carcinomas (NECs) represent relatively rare and heterogeneous malignancies. They are the most common group among neuroendocrine tumors (NETs). In most cases they are advanced at diagnosis and slow-growing, therefore conditioning a better prognosis compared with non neuroendocrine carcinomas from the same sites. No standard medical therapy exists, except for somatostatin analogs in functioning tumors, and octreotide LAR in functioning or non functioning well differentiated NECs from small bowel. Several systemic therapeutic options exist, including chemotherapy, somatostatin analog, interferon, peptide receptor radionuclide therapy (PRRT), and molecular targeted drugs. Among them some therapies have specific biological tumor targets and can be defined as " biological targeted therapies" This review focuses on the status of EP NECs targeted therapies in the light of recent advances. Somatostatin receptors (SSTRs) are the first therapeutic target detected in EP NECs. Through them SS analogs and PRRT act, producing symptomatic, biochemical, and, to a lesser extent, antiproliferative effects. New SS analogs, covering a higher number of SSTR subtypes, were developed, including pasireotide (SOM230), which controls 25% of carcinoid syndromes resistant to full dose octreotide LAR. Chimeric analogs, which bind SSTR2/SSTR5 and dopamine-2 receptor subtype (D2), are in preclinical phase of development. Among the numerous molecular targeted agents investigated in NETs, mTOR inhibitors and VEGF/VEGFR/PDGFR inhibitors are in most advanced clinical phase of investigation. In particular, everolimus, sunitinib, and bevacizumab are all studied in phase III trials. Both everolimus and sunitinib produced significant survival benefit versus placebo in advanced progressing well-differentiated pancreatic NECs. Sunitinib data have been presented at the last ASCO in June 2010, and everolimus data will be presented at next ESMO in September 2010.
KW - NEC
KW - Targeted therapy
UR - http://www.scopus.com/inward/record.url?scp=78649754940&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649754940&partnerID=8YFLogxK
U2 - 10.1016/S0305-7372(10)70026-8
DO - 10.1016/S0305-7372(10)70026-8
M3 - Article
C2 - 21129617
AN - SCOPUS:78649754940
VL - 36
JO - Cancer Treatment Reviews
JF - Cancer Treatment Reviews
SN - 0305-7372
IS - SUPPL. 3
ER -