High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial

Abstract

Objective: In acromegaly, 25-50% of patients respond inadequately to conventional long-acting somatostatin analogue (SSA) therapy. Response may be improved by increasing SSA frequency or dose. This study evaluated the biochemical efficacy and safety of high-dose octreotide in patients with acromegaly. Design: A 24-week prospective, multicentre, randomised, open-label trial conducted from 12 December 2005 to 23 October 2007 in patients with persistently uncontrolled acromegaly despite R6 month conventional SSA therapy. Methods: Patients with R50% reduction in GH levels during previous SSA treatment were randomised to high-dose (60 mg/28 days) or high-frequency (30 mg/21 days) octreotide i.m. injection. Primary end-points were week 12 and 24 reduction in serum IGF1 and GH from baseline. Secondary end points included IGF1 normalisation and tumour shrinkage rates, and safety/tolerability evaluations. Results: Significantly, more patients (10 out of 11) achieved week 24 IGF1 reduction in the high-dose than the high-frequency group (8 out of 15; P!0.05). In the high-dose group only, week-24 IGF1 values were significantly reduced (PZ0.02) versus baseline. Normalisation of IGF1 occurred only with the high-dose regimen (4/11; PZ0.02). Out of 14 patients experiencing adverse events, 5 reported drug-related gastrointestinal effects. No dose-response relationship was seen. Safety parameters were similar between treatment groups, apart from a slight decrease in HbA1c in the high-dose group only. Conclusion: High-dose octreotide treatment is safe and effective (normalisation of IGF1 levels) in a subset of patients with active acromegaly inadequately controlled with long-term SSA. Individualised octreotide doses up to 60 mg/28 days may improve outcomes of SSA therapy.

Effects of high-dose octreotide LAR on glucose metabolism in patients with acromegaly inadequately controlled by conventional somatostatin analog therapy

“…This post-hoc analysis was performed on 26 patients with persistently uncontrolled acromegaly under maximal conventional SSA doses, who had been enrolled in a prospective multicenter, randomized, controlled, open-label study, the results of which have been published recently (11). The protocol was approved by the ethical committee of the Principal Investigator (A G: ethical committee of Spedali Civili di Brescia on behalf of the National Health Authority) and by all local ethical committees of each participating center.…”

“…The study was preregistered at ClinicalTrials.gov; registration number: NCT00372697. The inclusion and exclusion criteria are detailed in the original publication (11).…”

“…A recent randomized study has demonstrated that high doses of octreotide LAR are well tolerated and effective in normalizing IGF1 in a subset of patients with acromegaly that were previously inadequately controlled by conventional SSA therapy (11). In the present study, we performed a post-hoc analysis of the glycometabolic data acquired during this trial.…”

Expert consensus document: A consensus on the medical treatment of acromegaly

“…6,64 In patients demonstrating clear decreases in GH/IGF-I levels (but in whom these levels are not normalized) when treated with the highest approved SRL doses, further dose increases or a decrease in injection interval can be considered (DR). [65][66][67] In patients with well-controlled acromegaly during SRL therapy, a decrease in SRL administration to the minimally effective dose can be considered (DR). If both biochemical and clinical disease control are maintained with the minimal dose of SRL, an increased dose interval (up to every 3 months) can be considered (DR).…”

Safety review: Dose optimization of somatostatin analogs in patients with acromegaly and neuroendocrine tumors

“…43 LAR to achieve control of GH (<2 μg/L) and normalization of IGF-1. 44 Overall, high-dose treatment with octreotide LAR controlled Previously, NET were divided into three subtypes (foregut, midgut, and hindgut) based on their embryologic origin (Table 2A); 48,49 however, recently the practice has changed to classify the tumors based on the location of primary origin, differentiation/tumor-node-metastasis (TNM)…”