Conceptos Categóricos

REVISION ACERCA DEL ENFOQUE DE LOS TUMORES NEUROENDOCRINOS BIEN DIFERENCIADOS

REVISION ACERCA DEL ENFOQUE DE LOS TUMORES NEUROENDOCRINOS BIEN DIFERENCIADOS

(especial para SIIC © Derechos reservados)
Se presenta una actualización del enfoque diagnóstico y el abordaje terapéutico de las neoplasias neuroendocrinas bien diferenciadas, incluidos los tumores carcinoides y las variantes de localización pancreática, con hincapié en las aplicaciones de las nuevas terapias moleculares dirigidas.
Autor:
Diane Reidy-lagunes
Columnista Experta de SIIC

Institución:
Memorial Sloan-Kettering Cancer Center


Artículos publicados por Diane Reidy-lagunes
Coautor
Ed Wyluda* 
DO, Memorial Sloan-Kettering Cancer Center, Nueva York, EE.UU.*
Recepción del artículo
26 de Abril, 2011
Aprobación
12 de Julio, 2011
Primera edición
29 de Septiembre, 2011
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Los tumores neuroendocrinos bien diferenciados (TNE) son neoplasias malignas poco frecuentes que incluyen tanto los carcinoides como los tumores neuroendocrinos pancreáticos (TNEP). Estos tumores se asocian en general con metástasis en el momento del diagnóstico. Si bien la supervivencia prolongada es frecuente, la supervivencia global se reduce de manera acentuada cuando los pacientes presentan síntomas, así como cuando el tumor progresa pese a la terapia con análogos de la somatostatina. Aunque estos fármacos pueden contribuir a tratar la sintomatología y ralentizar el crecimiento tumoral, en especial en neoplasias de bajo grado, no se ha demostrado que el tratamiento a largo plazo sea eficaz en estos pacientes. Recientemente, los ensayos preclínicos y dos estudios de fase III han brindado avances promisorios, sobre todo en el tratamiento de los TNEP. La aparición de terapias dirigidas contra el factor de crecimiento vascular endotelial (VEGF), los inhibidores de la diana de la rapamicina (mTOR) y el tratamiento con receptores de péptidos radiomarcados se ha asociado con eficacia moderada, pero pueden vincularse con toxicidad relevante. En esta revisión, discutiremos los ensayos recientes y las terapias actuales de los TNE bien diferenciados.

Palabras clave
tumores neuroendocrinos bien diferenciados, tumor neuroendocrino pancreático, carcinoide


Artículo completo

(castellano)
Extensión:  +/-9.99 páginas impresas en papel A4
Exclusivo para suscriptores/assinantes

Abstract
Well-differentiated neuroendocrine tumors (NETs) are uncommon malignancies consisting of both carcinoid and pancreatic neuroendocrine tumors (pNETs). These tumors are usually associated with metastasis when diagnosed. Although prolonged survival is common, overall survival decreases substantially when a patient becomes symptomatic and when the tumor progresses on somatostatin analog therapy. While somatostatin analogs can help to treat symptomatology and slow tumor growth mainly in low grade tumors, there have been no proven long term treatments to effectively aid these patients. Recently, two phase III trials along with pre clinical studies have provided promising advancements, mainly in the treatment of pNETs. The emergence of targeted therapies consisting of vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) inhibitors and peptide receptor radiolabeled therapy (PRRT) have demonstrated modest efficacy but can result in non-trivial toxicities. In this review we will discuss recent trials and current therapies for well-differentiated NETs.

Key words
well-differentiated neuroendocrine tumors, pancreatic neuroendocrine tumor, carcinoid


Full text
(english)
para suscriptores/ assinantes

Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Oncología
Relacionadas: Anatomía Patológica, Diagnóstico por Imágenes, Diagnóstico por Laboratorio, Endocrinología y Metabolismo, Farmacología, Gastroenterología, Geriatría, Medicina Farmacéutica, Medicina Interna, Medicina Nuclear



Comprar este artículo
Extensión: 9.99 páginas impresas en papel A4

file05.gif (1491 bytes) Artículos seleccionados para su compra



Enviar correspondencia a:
Diane Reidy-Lagunes, Memorial Sloan-Kettering Cancer Center, NY 10065, 275 York Avenue, Room H-917, Nueva York, EE.UU.
Bibliografía del artículo
1. Rindi G, D'Adda T, Froio E et al. Prognostic factors in gastrointestinal endocrine tumors. Endocr Pathol 18:145-9, 2007.
2. Ferrone C, Tang L, Tomplinson J, et al editors. Pancreatic neuroendocrine tumors: Can the WHO staging system be simplified. ASCO, Chicago, 2007.
3. Van Eeden S, Quadvlieg P, Babs G, et al. Classification of low-grade neuroendocrine tumors of midgut and unknown origin. Hum Pathol 33:1126-32, 2002.
4. Moertel C, Kvols L, O'Connell M, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin: evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer 68:227-32, 1991.
5. Jiao Y, Shi C, Edil BH, de Wilde RF, Klimstra DS, Maitra A, et al. DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science 331(6021):1199-203, 2011.
6. Lamberts S, Bakker W, Reubi J, Krenning E. Somatostatin-receptor imaging in the localization of endocrine tumors. N Engl J Med 323:1246-9, 1990.
7. Reidy-Lagunes, DL, Gollub M, Saltz, L. Addition of octreotide functional imaging to cross-sectional computed tomography or magnetic resonance imaging for the detection of neuroendocrine tumors: Added value or an anachronism? Journal of Clinical Oncology 32.8559 , 2010 (correspondence).
8. Asnacios A, Courbon F, Rochaix P, et al. Indium-111-pentetreotide scintigraphy and somatostatin receptor subtype 2 expression: New prognostic factors for malignant well-differentiated endocrine tumors. Journal of Clinical Oncology 26(6):963-70, 2008.
9. Reubi J, Kvols L, Waser B et al. Detection of somatostatin receptors in surgical and percutaneous needle biopsy samples of carcinoids and islet cell carcinomas. Cancer Res 50:5969-77, 1990.
10. Kvols LK MC, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome: evaluation of a long-acting somatostatin analogue. N Engl J Med 315:663-6, 1986.
11. Di Bartolomeo M, Bajetta E, Buzzoni R, et al. Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors: a study by the Italian Trials in Medical Oncology Group. Cancer 77:402-8, 1996.
12. Ruszniewski P, Ducreux M, Chayvialle J, et al. Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients. Gut 39:279-83, 1996.
13. Faiss S, Rath U, Mansmann U, et al. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system. Recent Results Cancer Res 142:193-207, 1996.
14. Weslin S, Janson E, Sundin A. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumors. Eur J Endocrinol 151(1):107-12, 2004.
15. Arnold R, Benning R, Neuhaus C, et al. Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. Digestion 54(Suppl. 1):72-5, 1993.
16. Saltz L TB, Buckley M, et al. Octreotide as an antineoplastic agent in the treatment of functional and non-functional neuroendocrine tumors. Cancer 72:244-8, 1993.
17. Ducreux M, Ruszniewski P, Chayvialle J, et al. The antitumoral effect of the long-acting somatostatin analog lanreotide in neuroendocrine tumors. Am J Gastroenterol 95:3276-81, 2000.
18. Rinke A, Muller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27(28):4656-63, 2009.
19. Duran I, Kortmansky J, Singh D, et al. A phase II clinical and pharmacodynamic study trial of temsirolimus in advanced neuroendocrine tumors. British Journal of Cancer 95:1148-54, 2006.
20. Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, et al. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol 28(1):69-76, 2010.
21. Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364(6):514-23, 2011.
22. Yao JC, Hainsworth JD, Baudin E, Peeters M, Hoersch D, Anthony LB, et al. Everolimus plus octreotide LAR (E+O) versus placebo plus octreotide LAR (P+0) in patients with advanced neuroendocrine tumors (NET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-2). J of Clin Oncol 29(Suppl. 4; abstr. 159), 2011.
23. Terris B, Scoazec J, Rubbia L, et al. Expression of vascular endothelial growth factor in digestive tumours. Histopathology 32:133-8, 1998.
24. Phan A, Wang L, Xie K, et al., editors. Association of VEGF expression with poor prognosis among patients with low-grade neuroendocrine carcinoma. Annual Meeting of American Society of Clinical Oncology, Atlanta, 2006.
25. Hurwitz H, Fehrenbacher L, Novotyn W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335-42, 2004.
26. Kulke M, Stuart K, Earle C, et al., editors. A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors. Proceedings ASCO, Atlanta, GA, 2006.
27. Kulke M, Lenz H, Meropol N, et al. Results of a phase II study with sunitinib malate (SU11248) in patients with advanced neuroendocrine tumours. European Journal Cancer, 2005.
28. Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364(6):501-13, 2011.
29. Walderr C, Pless M, Maecke H, et al. The clinical value of [90Y-DOTA]-dPhe-Tyr-octreotide in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 12:941-5, 2011.
30. Waldherr C, Pless M, Maecke H, et al Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. J Nucl Med 43(5):610-6, 2002.
31. Virgolini I, Britton K, Buscombe J, et al. 111In- and 90Y-DOTA-Lanreotide: Results and implications of the MAURITIUS trial. J Nucl Med 32(2):148-55, 2002.
32. Valkema R, Pauwels S, Kvols L, et al. Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0,Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 36:147, 2006.
33. Kwekkeboom D, Wouter W, De Herder B, et al. Treatment With the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. Journal of Clinical Oncology 26(13):2124-30, 2008.
34. Kwekkeboom J, Teunissen J, Bakker WH ea. Treatment with the radiolabeled somatostatin analogue [177Lu-DOTA°,Tyr3]octreotate in patients with gastro-entero-pancreatic (GEP) tumors. J Clin Oncol 23:2754-62, 2005.
35. Cheng P, Saltz L. Failure to confirm major objective antitumor activity for streptozocin and doxorubicin in the treatment of patients with advanced islet cell carcinoma. Cancer 86(6):944-8, 1999.
36. Ramanathan R, Cnaan A, Hahn R, et al. Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol 12(8):1139-43, 2001.
37. Bukowski R, Tangen C, Peterson R, et al. Phase II trial of dimethyltriazenoimidazole carboxamide in paitents with metastatic carcinoid. A Southwest Oncology Group Study. Cancer 73:1505-8, 1994.
38. Sun W, Lipsitz S, Catalano P, et al. Phase II/III study of doxorubicin with fluorouracil compared with streptozocin with fluorouracil or dacarbazine in the treatment of advanced carcinoid tumors: Eastern Cooperative Oncology Group Study E1281. J Clin Oncol 23:4897-904, 2005.
39. Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer 117(2):268-75, 2011.
40. Kulke M, Frauenhoffer C, Hooshmand D, Ryan P, et al, editors. Prediction of response to temozolamide (TMZ)-based therapy by loss of MGMT expression in patients with advanced neuroendocrine tumors (NET). Proceedings ASCO, Chicago, IL, 2007.
41. Moertel C, Hanley J. Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome. Cancer Clin Trials 2:327-34, 1979.
42. Engstrom P, Lavin P, Moertel CG ea. Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor J Clin Oncol 2(11):1255-59, 1984.
43. Bukowski R, Johnson K, Peterson R, et al A phase II trial of combination chemotherapy in patients with metastatic carcinoid tumors. A Southwest Oncology Group Study. Cancer 60(12):2891-5, 1987.
44. Kulke MH, Siu LL, Tepper JE, Fisher G, Jaffe D, Haller DG, et al. Future Directions in the Treatment of Neuroendocrine Tumors: Consensus Report of the National Cancer Institute Neuroendocrine Tumor Clinical Trials Planning Meeting. J Clin Oncol, Jan 24, 2011.

 
 
 
 
 
 
 
 
 
 
 
 
Está expresamente prohibida la redistribución y la redifusión de todo o parte de los contenidos de la Sociedad Iberoamericana de Información Científica (SIIC) S.A. sin previo y expreso consentimiento de SIIC.
ua31618
-->