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GI-NEUROENDOCRINE TUMORSTHERAPEUTIC APROACHES
Chemotherapy:older and recent schemes
Ilias Athanasiadis, MD
Medical Oncologist
Director of the Oncology Department
MITERA Hospital, HYGEIA
Athens, July 5, 2014
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First‐line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas
CancerVolume 117, Issue 2, pages 268-275, 7 SEP 2010 DOI: 10.1002/cncr.25425http://onlinelibrary.wiley.com/doi/10.1002/cncr.25425/full#fig2
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First‐line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas
CancerVolume 117, Issue 2, pages 268-275, 7 SEP 2010 DOI: 10.1002/cncr.25425http://onlinelibrary.wiley.com/doi/10.1002/cncr.25425/full#fig3
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First‐line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas
CancerVolume 117, Issue 2, pages 268-275, 7 SEP 2010 DOI: 10.1002/cncr.25425http://onlinelibrary.wiley.com/doi/10.1002/cncr.25425/full#fig4
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Representative MGMT staining in carcinoid and pancreatic neuroendocrine tumors.
Kulke M H et al. Clin Cancer Res 2009;15:338-345
©2009 by American Association for Cancer Research
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PFS and OS for carcinoid and pancreatic neuroendocrine tumor patients treated with temozolomide-based therapy.
Kulke M H et al. Clin Cancer Res 2009;15:338-345
©2009 by American Association for Cancer Research
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PFS and OS in patients with MGMT-intact or MGMT-deficient neuroendocrine tumors treated with temozolomide-based therapy.
Kulke M H et al. Clin Cancer Res 2009;15:338-345
©2009 by American Association for Cancer Research
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Challenging issues
• Tumor heterogeneity• Tumor evolution and clone selection• Adaptation to therapy• The importance of the stroma• The host
immune surveillance and immune tolerance
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Following and understanding the tumor evolution
• Biomarkers as prognostic and predictive markers
• Circulating tumor cells• Next generation sequencing in
sequential specimens
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Figure 1
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
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Figure 3
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
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Figure 6
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
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Conclusion • Chemotherapy is active in advanced
pancreatic NETs • Alkylating agents has been the main
pillar of systemic chemotherapy• Streptozotocin application is based on
experience and studies from the past, but toxicity is a limitation
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Conclusion
• Temozolomide, capecitabine and combinations with bevacizumab demonstrate promising results challenging the current “standard”
• Activity in carcinoid tumors is modest• Individualization of therapy and
biomarkers represent a promising direction