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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
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
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
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
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
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
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
Challenging issues
• Tumor heterogeneity• Tumor evolution and clone selection• Adaptation to therapy• The importance of the stroma• The host
immune surveillance and immune tolerance
Following and understanding the tumor evolution
• Biomarkers as prognostic and predictive markers
• Circulating tumor cells• Next generation sequencing in
sequential specimens
Figure 1
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
Figure 3
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
Figure 6
Cell 2011 144, 646-674DOI: (10.1016/j.cell.2011.02.013) Copyright © 2011 Elsevier Inc. Terms and Conditions
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
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