CLINICAL EFFECTS OF OCTREOTIDE COMPARED TO PLACEBO IN PATIENTS WITH GASTROINTESTINAL NEUROENDOCRINE TUMORS - REPORT ON A DOUBLE-BLIND, RANDOMIZED TRIAL

Objectives. To compare the effect of octreotide with placebo on symptoms, tumour marker and quality of life in patients with gastrointestinal neuroendocrine tumours and liver metastases. Design. A blinded, placebo-controlled, cross-over study was performed. The number of Bushing epidodes and diarrhoea episodes were registered for 1 week prior to the study and for the 8-week duration of the study. Quality of life and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) excretion were measured before-the start, and at 4 and 8 weeks. Quality of life was registered with the Psychosocial Adjustment to Illness Scale (PAIS) and 5-HIAA measured by high-performance chromatography with electrochemical detection. 5-HIAA values exceeding 45 mu mol 24 h(-1) were considered to be elevated. Setting. The study was performed in a tertiary referral centre. Subjects. Twelve patients were approached; eleven patients were included, with a mean age of 56.5 (range 30-72) years. The primary tumour originated from the small intestine in nine and from the pancreas in two patients. The main symptoms were diarrhoea, Bushing and nausea, The 24-h excretion of 5-HIAA was increased in all patients. Interventions. Patients were treated for 4 weeks with octreotide (100 mu g) subcutaneously, twice daily, and for 4 weeks on placebo (octreotide vehicle) in random starting order. Main outcome measures. The main outcome measures were the number of episodes of the main clinical symptom(s) and 24-h 5-HIAA excretion. Results. Octreotide lowered diarrhoea and Bushing frequency significantly compared to placebo. 5-HIAA excretion was reduced during treatment with the active drug. Two domains of the PAIS were significantly improved, indicating that the reduction of tumour marker and symptoms were clinically important. Conclusions. The clinical effect of octreotide on symptoms in patients with neuroendocrine tumours was demonstrated in a controlled, prospective trial.