gi-neuroendocrine tumors therapeutic aproaches chemotherapy: older and recent schemes ilias...

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