9. Pharmacological Therapy of Neuroendocrine Tumors

Abstract

Somatostatin analogs are currently indicated for the relief of symptoms associated with hypersecretion syndromes in patients with gastroenteropancreatic neuroendocrine tumors (NETs). However, antiproliferative efficacy of somatostatin analogs is still debated. In patients with metastatic well-differentiated neuroendocrine tumors (NETs), antiproliferative treatment is intended to reduce tumor burden, delay tumor progression and prolong survival. Available antiproliferative treatment options include surgical, ablative, radiotherapeutic, and pharmacological strategies, most of which are associated with adverse effects that can compromise quality of life. Somatostatin analogs are associated with minimal adverse effects. For this reason, they have been offered to patients with metastatic disease not amenable to surgery. However, the ability of somatostatin analogs to control tumor growth remains controversial. Antiproliferative effects have been reported in uncontrolled in vivo and in vitro studies1,2, including early case reports where tumor shrinkage and even tumor disappearance were shown. In prior studies on antiproliferative effects of somatostatin analogs in NET patients, tumor stabilization was demonstrated in about half of the patients but only very few objective responses (≤5%) were observed3-10. Some limitations of these prior trials have to be taken into consideration: None of these studies was placebo controlled and limited number of patients (range, 15-50 patients) was included; most of them included a heterogeneous patient population presenting with NETs of different origin and biological behaviour. Furthermore, these studies did not include treatment-naive patients and different dosages/formulations of somatostatin analogs were used. Given these considerations, one could argue that the observed disease stabilization may reflect the course of the disease rather than the effect of treatment. The PROMID study11 was conducted to evaluate antiproliferative efficacy of 30 mg octreotide LAR in a wellTumori, 96: 847-857, 2010