Dose escalation of octreotide LAR is safe and effective in patients with advanced gastrointestinal neuroendocrine tumours for control of symptoms and tumor progression

Octreotide is a powerful drug for patients with gastroentero-pancreatic neuroendocrine tumors (GEP- NET). We recently reviewed in this Journal the role of somatostatin analogs as antiproliferative agents, but so far no results from randomized controlled trials were available (1). Meanwhile, the PROMID-study has estab- lished that a monthly dose of 30 mg octreotide-Long Acting Release (LAR) controls tumor growth in patients with advanced midgut neuroendocrine tumors, resulting in an important benefit in progression free survival com- pared to placebo (14.3 versus 6 months, hazard ratio = 0.34 ; 95% CI, 0.20 to 0.59 ; p = 0.000072) (2). It is important to recall that this somatostatin analogue main- ly exerts its actions through the somatostatin-2 and 3- receptors, but saturation is incomplete at the classical doses of octreotide-LAR of up to 30 mg monthly (3). Symptoms of carcinoid syndrome have been reported to respond in only 50% of cases to the standard dose of octreotide-LAR (4). However, a prospective study reported an improved effect of a high-dose treatment with octreotide pamoate in patients with advanced malignant midgut carcinoid tumours (5). In this study, 12 patients received doses of octreotide of 160 mg every 2-4 weeks resulting in 75% of patients with tumour growth stabilisation for a median of 12 months and the majority of patients experiencing an amelioration of symptoms.