1703IN - Implications for clinical practice and trial design

Date 29 September 2012
Event ESMO Congress 2012
Session Integrating targeted treatments with tumor biology and molecular imaging in the current and future management of neuroendocrine gastrointestinal tumors
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Presenter Kjell Oeberg
Authors K. Oeberg
  • Endocrine Oncology, University Hospital Uppsala Akademiska Sjukhuset, 751 85 - Uppsala/SE

Abstract

Neuroendocrine GI tumors have demonstrated increase in incidence and prevalence during the last decades, reaching an incidence of 6/100,000 population recently. One of the reasons for the increasing incidence and prevalence is greater awareness among physicians about these conditions but also a better diagnosis and treatment. Development of specific biomarkers, such as chromogranin A both for histopathology and marker in the circulation, facilitate the establishment of correct diagnosis and can also be used for follow-up of the patient. Molecular imaging is another important step forward including somatostatin receptor scintigraphy, Gallium-68 DOTATATE, PET/CT as well as more specific PET-tracers such as C11-5HTP and GLP1 binding tracers. Molecular images are not only for localisation of the disease, but also for staging and of course also give information about the metabolism and tumor biology. For several decades biotherapy has been applied in patients with slow-growing NETs including somatostatin analogs and alpha interferon. The tumor cells express specific receptors for somatostatin as well as interferon. In recent days targeted treatment has been instituted with tyrosine kinase and mTOR inhibitors. These treatments have been particular useful for pancreatic NETs where preclinical evaluation of a single transduction pathways, such as IGF1 receptor signalling as well as the mTOR signalling pathway has been explored and demonstrated to be activated in many of these tumors. In recent years peptide receptor radiotherapy based on somatostatin analogs, such as 177Lutetium DOTATATE and 90Yttrium DOTATOC has been applied in NETs with significant antitumor effect and prolongation of survival. In the future the treatment will be based on tumor biology, molecular genetics and thereby aiming at personalized medicine. It will include combinations of new cytotoxic therapies (temozolomide, capecitabine) together with targeted agents such as sunitinib and everolimus, but also combined with PRRT.

Disclosure

K. Oeberg: Advisory Board: Ipsen, Novartis. Speakers Buerau: Ipsen, Novartis, Pfizer