Cancer research has been intensively searching for treatment strategies which target and inhibit specific "overactive" signal pathways or proteins in the tumor. Thanks to the targeted or "tailored" switching off of the growth program in the tumor cell, specific therapies can be developed. Carcinoids have become a model disease for targeted therapy, as they express so-called somatostatin receptors at a high density on the surface of their well-differentiated, neuroendocrine tumor cells. For the last 25 years somatostatin receptors (docking sites for somatostatins) have formed the basis for targeted or tailored treatment strategies of neuroendocrine tumors.

Somatostatin is a natural hormone. It circulates in the body in physiological amounts and performs various tasks. Due to its rapid breakdown the natural somatostatin is not suitable for the long-term therapy of carcinoid disease. A major therapeutic breakthrough occurred at the beginning of the 1990s, when long-acting depot preparations of stabile somatostatin analogs could be produced. Today these depot preparations are injected once every four weeks, either deep subcutaneously or in the muscle of the buttocks. As mentioned above, somatostatin derivatives (so-called somatostatin analogs like octreotide or lanreotide) are the therapy of choice for the carcinoid syndrome.

In 2009, a controlled prospective phase III study (PROMID study) showed that the octreotide depot preparation (30 mg octreotide LAR) significantly prolonged the (progression-free) survival of patients with midgut carcinoids. The PROMID study was the first phase III-trial on advanced intestinal carcinoids to show a survival benefit of drug therapy (octreotide) versus placebo. Interestingly, the survival benefit was particularly pronounced in those carcinoid patients who had a low tumor load in the liver. This observation supports the recommendation to combine somatostatins with liver-directed treatment modalities which effectively reduce, destroy or eliminate neuroendocrine liver metastases. Multimodal therapy is the standard treatment of neuroendocrine liver metastases. Multimodal therapy means the (sequential) combination of different treatment strategies in an individual patient.

In 2013, a controlled prospective phase III study (CLARINET study) showed that the lanreotide depot preparation (120 mg lanreotide) significantly prolonged the (progression-free) survival of patients with well-differentiated (G1, G2 and Ki-67<10%), neuroendocrine tumors. The CLARINET study is the first phase III-trial to demonstrate a survival benefit of a somatostatin analog not only in patients with non-functional midgut carcinoids but also in patients suffering from well-differentiated, non-functional neuroendocrine tumors of the pancreas. It appears very likely that somatostatin analogs will receive accelerated approval for the treatment of advanced, non-functional midgut carcinoids and of advanced well-differentiated (Ki-67 < 10%), non-functional neuroendocrine tumors of the pancreas. Future studies will evaluate the safety and therapeutic potential of somatostatin analogs in neuroendocrine tumors of other organs or even in patients with mixed adenoneuroendocrine carcinomas (MANEC). Thus, both octreotide and lanreotide provide survival benefit and hope to patients living with neuroendocrine tumor disease.

Contact

Center of Neuroendocrine Tumors
Prof. Dr. med. Hans Scherübl
Vivantes Klinikum Am Urban
Academic Teaching Hospital of Charité-University Medicine, Berlin
Dieffenbachstraße 1
10967 Berlin, Germany
Tel: + 49 30 130 225201
Fax: + 49 30 130 225205
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.
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