75IN - Peptide receptor radionuclide therapy of neuroendocrine tumours

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 Lisa Bodei
Authors L. Bodei1, C.M. Grana2, M. Cremonesi2, G. Paganelli2
  • 1Nurclear Medicine Division, European Institute of Oncology, 20141 - Milan/IT
  • 2Nuclear Medicine, European Institute of Oncology, 20141 - Milano/IT

Abstract

In the past two decades a new approach to neuroendocrine tumors based on specific receptor targeting was introduced in the clinical practice. Peptide receptor radionuclide therapy (PRRT) consists in the systemic administration of a synthetic analogue, radiolabelled with a suitable beta-emitting radionuclide. These compounds are able to irradiate tumors and their metastases via the internalization through a specific receptor subtype, generally over-expressed on the cell membrane. Pre-clinical studies have indicated many potential receptor candidates for PRRT. To date, the mostly exploited system is the somatostatin-somatostatin receptor. PRRT can deliver high absorbed doses to tumors, adequate to achieve significant volume reduction. Treatment with radiolabeled somatostatin analogues, such as [90Y-DOTA0,Tyr3]-octreotide (or 90Y-DOTATOC) and [177Lu-DOTA0,Tyr3]-octreotate (or 177Lu-DOTATATE), is an efficient new tool in the management of patients with inoperable or metastasized gastro-entero-pancreatic (GEP) neuroendocrine tumors. Clinical trials performed in several countries, despite different phase I-II protocols, showed complete and partial responses in 10 to 30% of patients for 90Y-DOTATOC. In the clinical trial with 177Lu-DOTATATE, 47% overall response rate was observed, with a median time to progression of >36 months and a significant impact on survival. FDG PET evaluation is useful to predict progression free survival to PRRT in G1/G2 neuroendocrine tumors. Significant biochemical and symptomatic responses in functioning tumors were encountered for both radiopeptides. Toxicity, requiring renal-protective agents, is generally mild and may involve kidneys and bone marrow. These data indicate that PRRT is a convincing therapeutic tool in the treatment scenario of GEP tumors. Newer strategies to increase the therapeutic potential of PRRT, such as the combination with radiosensitizing chemotherapy, are presently under investigation. Incoming phase III protocols comparing PRRT with 177Lu-DOTATATE versus conventional therapies will help clarifying the position of PRRT in the therapeutic algorithm of neuroendocrine tumors.

Disclosure

The author has declared no conflicts of interest.