Digestive and Liver Disease
Volume 44, Issue 2 , Pages 95-105 , February 2012

New treatment strategies in advanced neuroendocrine tumours

  • Thomas Walter

      Affiliations

    • Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Lyon CEDEX 03, France
    • Corresponding Author InformationCorresponding author at: Pavillon H, Hôpital Edouard Herriot, 69437 Lyon CEDEX 03, France.
    • ,
  • Hedia Brixi-Benmansour

      Affiliations

    • Service d’Hépato-Gastroentérologie et d’Oncologie Digestive, CHU Reims, Hôpital Robert Debré, Reims CEDEX, France
    • ,
  • Catherine Lombard-Bohas

      Affiliations

    • Fédération des Spécialités Digestives, Hôpital Edouard Herriot, Lyon CEDEX 03, France
    • ,
  • Guillaume Cadiot

      Affiliations

    • Service d’Hépato-Gastroentérologie et d’Oncologie Digestive, CHU Reims, Hôpital Robert Debré, Reims CEDEX, France

Received 19 July 2011 ,Accepted 23 August 2011.

References 

  1. Solcia E, Klöppel G, Sobin L. Histological typing of endocrine tumours. 2nd ed.. New York: Springer Verlag; 2000;
  2. Bosman FT, Carneiro F, Hruban RH, et al. WHO classification of tumors of the digestive system. 4th ed.. Lyon: IARC; 2010;
  3. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–3072
  4. Lepage C, Rachet B, Coleman MP. Survival from malignant digestive endocrine tumors in England and Wales: a population-based study. Gastroenterology. 2007;132:899–904
  5. Rindi G, Klöppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449:395–401
  6. Rindi G, Klöppel G, Couvelard A, et al. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2007;451:757–762
  7. Sobin L, Gospodarowicz M, Wittekind C UICC International Union Against Cancer. TNM classification of malignant tumours. Oxford: Wiley-Blackwell; 2010;
  8. Kulke MH, Siu LL, Tepper JE, 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. 2011;29:934–943
  9. Modlin IM, Oberg K, Chung DC, et al. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008;9:61–72
  10. Auernhammer CJ, Goke B. Therapeutic strategies for advanced neuroendocrine carcinomas of jejunum/ileum and pancreatic origin. Gut. 2011;60:1009–1021
  11. Oberg K, Ferone D, Kaltsas G, et al. ENETS consensus guidelines for the standards of care in neuroendocrine tumors: biotherapy. Neuroendocrinology. 2009;90:209–213
  12. Modlin IM, Pavel M, Kidd M, et al. Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2011;31:169–188
  13. Arnold R, Wied M, Behr TH. Somatostatin analogues in the treatment of endocrine tumors of the gastrointestinal tract. Expert Opin Pharmacother. 2002;3:643–656
  14. Kulke MH, Stuart K, Earle CC, et al. A phase II study of temozolomide and bevacizumab in patients with advanced neuroendocrine tumors. J Clin Oncol. 2006;24;Abstract 4044
  15. Kulke MH, Bergsland EK, Yao JC. Glycemic control in patients with insulinoma treated with everolimus. N Engl J Med. 2009;360:195–197
  16. Steinmuller T, Kianmanesh R, Falconi M, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2008;87:47–62
  17. Gurusamy KS, Pamecha V, Sharma D, et al. Palliative cytoreductive surgery versus other palliative treatments in patients with unresectable liver metastases from gastro-entero-pancreatic neuroendocrine tumours. Cochrane Database Syst Rev. 2009;CD007118
  18. Kianmanesh R, Sauvanet A, Hentic O, et al. Two-step surgery for synchronous bilobar liver metastases from digestive endocrine tumors: a safe approach for radical resection. Ann Surg. 2008;247:659–665
  19. Elias D, Goere D, Leroux G, et al. Combined liver surgery and RFA for patients with gastroenteropancreatic endocrine tumors presenting with more than 15 metastases to the liver. Eur J Surg Oncol. 2009;35:1092–1097
  20. Akyildiz HY, Mitchell J, Milas M, et al. Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery. 2010;148:1288–1293discussion 93
  21. Saxena A, Chua TC, Sarkar A, et al. Progression and survival results after radical hepatic metastasectomy of indolent advanced neuroendocrine neoplasms (NENs) supports an aggressive surgical approach. Surgery. 2011;149:209–220
  22. Cho CS, Labow DM, Tang L, et al. Histologic grade is correlated with outcome after resection of hepatic neuroendocrine neoplasms. Cancer. 2008;113:126–134
  23. Elias D, Lefevre JH, Duvillard P, et al. Hepatic metastases from neuroendocrine tumors with a “thin slice” pathological examination: they are many more than you think. Ann Surg. 2010;251:307–310
  24. Maire F, Hammel P, Faivre S, et al. Temozolomide: a safe and effective treatment for malignant digestive endocrine tumors. Neuroendocrinology. 2009;90:67–72
  25. Clark OH, Benson AB, Berlin JD, et al. NCCN clinical practice guidelines in oncology: neuroendocrine tumors. J Natl Compr Canc Netw. 2009;7:712–747
  26. Boudreaux JP, Klimstra DS, Hassan MM, et al. The NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the jejunum, ileum, appendix, and cecum. Pancreas. 2010;39:753–766
  27. Bettini R, Mantovani W, Boninsegna L, et al. Primary tumour resection in metastatic nonfunctioning pancreatic endocrine carcinomas. Dig Liver Dis. 2009;41:49–55
  28. Mathe Z, Tagkalos E, Paul A, et al. Liver transplantation for hepatic metastases of neuroendocrine pancreatic tumors: a survival-based analysis. Transplantation. 2011;91:575–582
  29. Le Treut YP, Gregoire E, Belghiti J, et al. Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report. Am J Transplant. 2008;8:1205–1213
  30. Strosberg JR, Cheema A, Kvols LK. A review of systemic and liver-directed therapies for metastatic neuroendocrine tumors of the gastroenteropancreatic tract. Cancer Control. 2011;18:127–137
  31. Mayo SC, de Jong MC, Bloomston M, et al. Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Ann Surg Oncol. 2011;(June):[Epub ahead of print]
  32. Marrache F, Vullierme MP, Roy C, et al. Arterial phase enhancement and body mass index are predictors of response to chemoembolisation for liver metastases of endocrine tumours. Br J Cancer. 2007;96:49–55
  33. Dong XD, Carr BI. Hepatic artery chemoembolization for the treatment of liver metastases from neuroendocrine tumors: a long-term follow-up in 123 patients. Med Oncol. 2011;(November):[Epub ahead of print]
  34. Vogl TJ, Gruber T, Naguib NN, et al. Liver metastases of neuroendocrine tumors: treatment with hepatic transarterial chemotherapy using two therapeutic protocols. AJR Am J Roentgenol. 2009;193:941–947
  35. de Baere T, Deschamps F, Teriitheau C, et al. Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results. J Vasc Interv Radiol. 2008;19:855–861
  36. Gaur SK, Friese JL, Sadow CA, et al. Hepatic arterial chemoembolization using drug-eluting beads in gastrointestinal neuroendocrine tumor metastatic to the liver. Cardiovasc Intervent Radiol. 2011;34:566–572
  37. Strosberg J, Kvols L. Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors. World J Gastroenterol. 2010;16:2963–2970
  38. Rinke A, Muller HH, Schade-Brittinger C, 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. 2009;27:4656–4663
  39. Dahan L, Bonnetain F, Rougier P, et al. Phase III trial of chemotherapy using 5-fluorouracil and streptozotocin compared with interferon alpha for advanced carcinoid tumors: FNCLCC-FFCD 9710. Endocr Relat Cancer. 2009;16:1351–1361
  40. Fazio N, de Braud F, Delle Fave G, et al. Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination?. Ann Oncol. 2007;18:13–19
  41. Pavel ME, Baum U, Hahn EG, et al. Efficacy and tolerability of pegylated IFN-alpha in patients with neuroendocrine gastroenteropancreatic carcinomas. J Interferon Cytokine Res. 2006;26:8–13
  42. Kwekkeboom DJ, de Herder WW, Krenning EP. Somatostatin receptor-targeted radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40:173–185
  43. Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–2423
  44. Kunikowska J, Krolicki L, Hubalewska-Dydejczyk A, et al. Clinical results of radionuclide therapy of neuroendocrine tumours with (90)Y-DOTATATE and tandem (90)Y/(177)Lu-DOTATATE: which is a better therapy option?. Eur J Nucl Med Mol Imaging. 2011;(May):[Epub ahead of print]
  45. Hentic O, Couvelard A, Rebours V, et al. Ki-67 index, tumor differentiation, and extent of liver involvement are independent prognostic factors in patients with liver metastases of digestive endocrine carcinomas. Endocr Relat Cancer. 2010;18:51–59
  46. Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992;326:519–523
  47. Delaunoit T, Ducreux M, Boige V, et al. The doxorubicin-streptozotocin combination for the treatment of advanced well-differentiated pancreatic endocrine carcinoma; a judicious option?. Eur J Cancer. 2004;40:515–520
  48. Kouvaraki MA, Ajani JA, Hoff P, et al. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004;22:4762–4771
  49. Cheng PN, Saltz LB. Failure to confirm major objective antitumor activity for streptozocin and doxorubicin in the treatment of patients with advanced islet cell carcinoma. Cancer. 1999;86:944–948
  50. McCollum AD, Kulke MH, Ryan DP, et al. Lack of efficacy of streptozocin and doxorubicin in patients with advanced pancreatic endocrine tumors. Am J Clin Oncol. 2004;27:485–488
  51. Fjallskog ML, Janson ET, Falkmer UG, et al. Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors. Neuroendocrinology. 2008;88:53–58
  52. Turner NC, Strauss SJ, Sarker D, et al. Chemotherapy with 5-fluorouracil, cisplatin and streptozocin for neuroendocrine tumours. Br J Cancer. 2010;102:1106–1112
  53. Strosberg JR, Fine RL, Choi J, et al. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011;117:268–275
  54. Kulke MH, Hornick JL, Frauenhoffer C, et al. O6-methylguanine DNA methyltransferase deficiency and response to temozolomide-based therapy in patients with neuroendocrine tumors. Clin Cancer Res. 2009;15:338–345
  55. Ekeblad S, Sundin A, Janson ET, et al. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007;13:2986–2991
  56. Walter T, Bruneton D, Cassier PA, et al. Evaluation of the combination 5-fluorouracil, dacarbazine, and epirubicin in patients with advanced well-differentiated neuroendocrine tumors. Clin Colorectal Cancer. 2010;9:248–254
  57. Brixi-Benmansour H, Jouve J, Mitry E, et al. Phase II study of first-line FOLFIRI for progressive metastatic well-differentiated pancreatic endocrine carcinoma (FFCD 0302). Dig Liv Dis. 2011;43:912–916
  58. 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. 2005;23:4897–4904
  59. Terris B, Scoazec JY, Rubbia L, et al. Expression of vascular endothelial growth factor in digestive neuroendocrine tumours. Histopathology. 1998;32:133–138
  60. Yao JC, Phan A, Hoff PM, et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol. 2008;26:1316–1323
  61. Kunz PL, Kuo T, Kaiser HL, et al. A phase II study of capecitabine, oxaliplatin and bevacizumab for metastatic or unresectable neuroendocrine tumors: preliminary results. J Clin Oncol. 2008;26;Abstract 15502
  62. Kulke MH, Chan JA, Meyerhardt JA, et al. A prospective phase II study of 2-methoxyestradiol administered in combination with bevacizumab in patients with metastatic carcinoid tumors. Cancer Chemother Pharmacol. 2010;(October):[Epub ahead of print]
  63. Besig S, Voland P, Baur DM, et al. Vascular endothelial growth factors, angiogenesis, and survival in human ileal enterochromaffin cell carcinoids. Neuroendocrinology. 2009;90:402–415
  64. Varker KA, Campbell J, Shah MH. Phase II study of thalidomide in patients with metastatic carcinoid and islet cell tumors. Cancer Chemother Pharmacol. 2008;61:661–668
  65. Kulke MH, Bergsland EK, Ryan DP, et al. Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol. 2006;24:3555–3561
  66. Kulke MH, Stuart K, Enzinger PC, et al. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006;24:401–406
  67. Kulke MH, Lenz HJ, Meropol NJ, et al. Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol. 2008;26:3403–3410
  68. Hobday TJ, Rubin J, Holen K, et al. MC044h, a phase II trial of sorafenib in patients (pts) with metastatic neuroendocrine tumors (NET): a phase II consortium (P2C). J Clin Oncol. 2007;25;Abstract 4504
  69. Phan AT, Yao JC, Fogelman DR, et al. A prospective, multi-institutional phase II study of GW786034 (pazopanib) and depot octreotide (sandostatin LAR) in advanced low-grade neuroendocrine carcinoma (LGNEC). J Clin Oncol. 2010;28;Abstract 4001
  70. Raymond E, Dahan L, Raoul JL, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:501–513
  71. Raymond E, Niccoli P, Raoul J, et al. Updated overall survival and progression-free survival by blinded independent central review of sunitinib versus placebo for patients with advanced unresectable pancreatic neuroendocrine tumors. J Clin Oncol. 2011;29;Abstract 4008
  72. Faivre S, Kroemer G, Raymond E. Current development of mTOR inhibitors as anticancer agents. Nat Rev Drug Discov. 2006;5:671–688
  73. Duran I, Kortmansky J, Singh D, et al. A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas. Br J Cancer. 2006;95:1148–1154
  74. Yao JC, Phan AT, Chang DZ, et al. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol. 2008;26:4311–4318
  75. Yao JC, Lombard-Bohas C, Baudin E, 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. 2010;28:69–76
  76. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011;364:514–523
  77. Pavel ME, Hainsworth J, Baudin E, et al. A randomized, phase III trial of everolimus+octreotide LAR vs placebo+octreotide LAR in patients with advanced neuroendocrine tumours (NET) (RADIANT-2). Ann Oncol. 2010;21;Abstract LBA8
  78. Eriksson B, Klöppel G, Krenning E, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumors—well-differentiated jejunal-ileal tumor/carcinoma. Neuroendocrinology. 2008;87:8–19
  79. Ramage JK, Goretzki PE, Manfredi R, et al. Consensus guidelines for the management of patients with digestive neuroendocrine tumours: well-differentiated colon and rectum tumour/carcinoma. Neuroendocrinology. 2008;87:31–39
  80. Falconi M, Plockinger U, Kwekkeboom DJ, et al. Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology. 2006;84:196–211
  81. Kulke MH, Anthony LB, Bushnell DL, et al. NANETS treatment guidelines: well-differentiated neuroendocrine tumors of the stomach and pancreas. Pancreas. 2010;39:735–752
  82. Anthony LB, Strosberg JR, Klimstra DS, et al. The NANETS consensus guidelines for the diagnosis and management of gastrointestinal neuroendocrine tumors (NETs): well-differentiated nets of the distal colon and rectum. Pancreas. 2010;39:767–774
  83. Oberg K, Akerstrom G, Rindi G, et al. Neuroendocrine gastroenteropancreatic tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2011;21:S223–S227
  84. Dominguez S, Denys A, Madeira I, et al. Hepatic arterial chemoembolization with streptozotocin in patients with metastatic digestive endocrine tumours. Eur J Gastroenterol Hepatol. 2000;12:151–157
  85. Gupta S, Yao JC, Ahrar K, et al. Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J. 2003;9:261–267
  86. Loewe C, Schindl M, Cejna M, et al. Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR Am J Roentgenol. 2003;180:1379–1384
  87. Roche A, Girish BV, de Baere T, et al. Prognostic factors for chemoembolization in liver metastasis from endocrine tumors. Hepatogastroenterology. 2004;51:1751–1756
  88. Strosberg JR, Choi J, Cantor AB, et al. Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control. 2006;13:72–78
  89. Granberg D, Eriksson LG, Welin S, et al. Liver embolization with trisacryl gelatin microspheres (embosphere) in patients with neuroendocrine tumors. Acta Radiol. 2007;48:180–185
  90. Ho AS, Picus J, Darcy MD, et al. Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors. AJR Am J Roentgenol. 2007;188:1201–1207
  91. Whitney R, Valek V, Fages JF, et al. Transarterial chemoembolization and selective internal radiation for the treatment of patients with metastatic neuroendocrine tumors: a comparison of efficacy and cost. Oncologist. 2011;16:594–601
  92. King J, Quinn R, Glenn DM, et al. Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer. 2008;113:921–929
  93. Rhee TK, Lewandowski RJ, Liu DM, et al. 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience. Ann Surg. 2008;247:1029–1035
  94. Kennedy AS, Dezarn WA, McNeillie P, et al. Radioembolization for unresectable neuroendocrine hepatic metastases using resin 90Y-microspheres: early results in 148 patients. Am J Clin Oncol. 2008;31:271–279
  95. Valkema R, De Jong M, Bakker WH, et al. Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Semin Nucl Med. 2002;32:110–122
  96. Anthony LB, Woltering EA, Espenan GD, et al. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Semin Nucl Med. 2002;32:123–132
  97. Nguyen C, Faraggi M, Giraudet AL, et al. Long-term efficacy of radionuclide therapy in patients with disseminated neuroendocrine tumors uncontrolled by conventional therapy. J Nucl Med. 2004;45:1660–1668
  98. Delpassand ES, Sims-Mourtada J, Saso H, et al. Safety and efficacy of radionuclide therapy with high-activity In-111 pentetreotide in patients with progressive neuroendocrine tumors. Cancer Biother Radiopharm. 2008;23:292–300
  99. Paganelli G, Bodei L, Handkiewicz Junak D, et al. 90Y-DOTA-D-Phe1-Try3-octreotide in therapy of neuroendocrine malignancies. Biopolymers. 2002;66:393–398
  100. Valkema R, Pauwels S, Kvols LK, 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. 2006;36:147–156
  101. Forrer F, Waldherr C, Maecke HR, et al. Targeted radionuclide therapy with 90Y-DOTATOC in patients with neuroendocrine tumors. Anticancer Res. 2006;26:703–707
  102. Cwikla JB, Sankowski A, Seklecka N, et al. Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Ann Oncol. 2010;21:787–794
  103. Pfeifer AK, Gregersen T, Gronbaek H, et al. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland. Neuroendocrinology. 2011;93:189–196
  104. Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA 0,Tyr3] octreotate: efficacy, and survival. J Clin Oncol. 2008;26:2124–2130
  105. Bushnell DL, O’Dorisio TM, O’Dorisio MS, et al. 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol. 2010;28:1652–1659
  106. Ramanathan RK, Cnaan A, Hahn RG, et al. Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Ann Oncol. 2001;12:1139–1143
  107. Bajetta E, Ferrari L, Procopio G, et al. Efficacy of a chemotherapy combination for the treatment of metastatic neuroendocrine tumours. Ann Oncol. 2002;13:614–621
  108. Bajetta E, Catena L, Procopio G, et al. Are capecitabine and oxaliplatin (XELOX) suitable treatments for progressing low-grade and high-grade neuroendocrine tumours?. Cancer Chemother Pharmacol. 2007;59:637–642
  109. Cassier PA, Walter T, Eymard B, et al. Gemcitabine and oxaliplatin combination chemotherapy for metastatic well-differentiated neuroendocrine carcinomas: a single-center experience. Cancer. 2009;115:3392–3399
  110. Ducreux MP, Boige V, Leboulleux S, et al. A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with pretreated gastroenteropancreatic well-differentiated endocrine carcinomas. Oncology. 2006;70:134–140

PII: S1590-8658(11)00331-8

doi: 10.1016/j.dld.2011.08.022

Digestive and Liver Disease
Volume 44, Issue 2 , Pages 95-105 , February 2012

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