Role of somatostatin analogs in the clinical management of non-neuroendocrine solid tumors

Abstract

The somatostatin analogs octreotide, lanreotide and RC-160 (vapreotide) are known to have direct and indirect antitumor effects. Direct effects include the arrest of tumor growth and stimulation of apoptosis, resulting in tumor shrinkage. Indirect antiproliferative effects may occur through antiangiogenesis, immunomodulatory effects and the suppression of tumor-stimulating growth factors. With a safety profile of somatostatin analogs established over 20 years of clinical use in the treatment of neuroendocrine tumors, somatostatin analogs are attractive therapeutic options for patients with non-neuroendocrine tumors. In early clinical trials of somatostatin analogs, however, some cancer patients responded well, while others showed a lack of benefit. This variability in clinical response may reflect the selective binding affinities of octreotide, lanreotide and RC-160, which bind with high affinity to just two of the five different somatostatin receptor subtypes. Treatment response may therefore depend on the specific receptor subtype(s) present in the tumor, the relative proportion of receptor(s) expressed on the tumor cell surface and the absolute quantity of each receptor subtype. Greater understanding of the role of somatostatin receptors, their binding affinities and modes of action has led to increased research into the use of somatostatin analogs, particularly octreotide, in cancer treatment as monotherapies, in combination with hormonal treatments and cytotoxic therapies, and in both adjuvant and neoadjuvant settings. A review of the literature suggests that the antitumor potential of somatostatin analogs should be investigated further and additional studies might determine how these analogs can best be used to improve the treatment of patients with non-neuroendocrine tumors.