Cabergoline add-on therapy in patients with uncontrolled acromegaly under somatostatin analogues – a multicenter, retrospective, cohort study of non-irradiated patients applying current criteria for disease control  

SA. Urwyler*^a (Dr), I. Samperi^a (Dr), K. Lithgow^a (Dr), A. Mavilakandy^b (Mr), M. Matheou^c (Mr), J. Ayuk^a (Dr), K. Bradley^d (Dr), A. Pal^c (Dr), NL. Reddy^b (Dr), N. Karavitaki^a (Dr)

^a Institute of Metabolism and Systems Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UNITED KINGDOM ; ^b Department of Diabetes and Endocrinology, University Hospitals of Leicester NHS Trust, Leicester Royal Infirmary, Leicester, UNITED KINGDOM ; ^c Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust, Oxford, UNITED KINGDOM ; ^d Department of Endocrinology, Bristol Royal Infirmary, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, UNITED KINGDOM

* Sandrine.urwyler@usb.ch

Introduction

In acromegaly not controlled by somatostatin analogue (SSA) treatment, add-on therapy with cabergoline is a potential approach. A small number of studies have reported on the success of this strategy, with IGF-1 normalisation rates between 42% and 60% during periods of 3-55.4 months. However, these studies have included patients previously irradiated confounding their results. Furthermore, data on the outcome of SSA+cabergoline combination by applying current disease control criteria (normal IGF-1 and GH<1mcg/L) are not available.

Our aim was to investigate efficacy of SSA+cabergoline combination therapy in non-irradiated patients with acromegaly not fully responding to SSA treatment alone.

Patients and methods

In this multicenter, retrospective cohort study, non-irradiated patients offered cabergoline add-on therapy for uncontrolled acromegaly to ongoing SSA therapy were identified from registries of four UK Pituitary centers (Birmingham, Bristol, Leicester and Oxford). Clinical, laboratory, imaging data were analyzed.

Results

Twenty-six patients were included (median age at diagnosis of acromegaly 47 years (range 21 - 83), 53.8% females, 24% prolactin-co-secreting tumours). Median duration of SSA therapy before cabergoline was 18 months (2-118). Seventeen patients were on lanreotide 90-120mg every 3 or 4 weeks sc and nine on octreotide LAR 20-40mg every 3-6 weeks im. Before starting cabergoline, IGF-1 levels were 1.70 (median)xupper limit of normal (ULN) (range 1.03-2.92).

Median duration of SSA+cabergoline was 36 months (4-139). Median weekly cabergoline dose at last review was 2.5 mg (0.5-4.5). Normal IGF-1 was achieved in 23% of patients with no difference in the latest weekly cabergoline dose between responders and non-responders [1.25mg (0.5-3) vs 3mg (0.5-4.5), respectively]. On regression analysis, IGF-1xULN before starting cabergoline or presence of prolactin co-secreting tumour were not related with achievement of normal IGF-1. GH<1mcg/L was found in 39% of the patients, whereas 17% had both normal IGF-1 and GH<1mcg/L.

Conclusions

In our cohort of non-irradiated patients with acromegaly, add-on cabergoline normalised IGF-1 in 23% of those on ongoing SSA therapy, with pre-cabergoline IGF-1xULN not related with this effect. This response rate was lower compared to previous reports, possibly due to the exclusion of irradiated patients. Only 17% of the patients achieved both optimal GH and IGF-1 levels.

The author has declared no conflict of interest.