BACKGROUND In the present study we investigated the efficacy and tolerability of i.m. octreotide acetate (octreotide LAR) in patients with metastatic neuroendocrine tumors (NETs) previously treated and failed on i.m. lanreotide. METHODS Fifteen patients (8 females, 7 males, median age 67 years, range 28-81 years) with metastatic NETs (8 endocrine pancreatic tumors, 7 midgut carcinoids) were enrolled in the study. All patients were in progressive disease (objective: 11 patients, symptomatic: 10 patients, biochemical: 11 patients) after treatment with slow release lanreotide, 30 mg every 14 days for a median time of 8 months (range 3-19 months). All patients had measurable disease; 12 patients had elevated serum and/or urine markers and 11 were symptomatic. Octreotide scintigraphy was positive in 13 of 15 patients. Octreotide LAR was administered as i.m. injection at the dose of 20 mg every four weeks until disease progression. RESULTS An objective partial response (PR) was documented in one patient (7%), no change (NC) in six (40%), and progressive disease (PD) in eight patients (53%). The PR was observed in one patient with non-functioning endocrine pancreatic tumor with progressive liver and lymph node metastases after 16 months of i.m. lanreotide therapy. The median duration of disease stabilization was 7.5 months (range 6-12+ months). The overall biochemical response rate was 41%, including CRs (33%) and PRs (8%); biochemical responses were observed in carcinoids as well as in endocrine pancreatic tumors; the median duration of response was 5 months for CRs and 7.5 months for PRs. The overall symptomatic response rate was 82%. The median duration of response for diarrhoea, abdominal pain, or both was 6.5 months (range 3-12+ months). Improvement in performance status (PS) was obtained in 5 of 11 patients with PS of 1 at study entry. Median duration of octreotide LAR treatment was seven months (range 3-12+ months). No serious adverse events were reported; mild side effects were reported in 26% of patients. CONCLUSIONS Octreotide LAR 20 mg shows significant efficacy in terms of objective response rate (PR + SD), biochemical and symptomatic control in patients with metastatic NETs of the GEP system pretreated and progressing on slow release lanreotide.