News

Round up from ENEA 2010, Liege, Belgium

23 Sep 2010

The European NeuroEndocrine Association (ENEA) 14th Congress in Liege, Belgium, had a high-impact and clinically insightful programme, providing a comprehensive update on research developments across neuroendocrinology. Among the several new and exciting developments in neuroendocrinology research were the recent advances in treatment options for acromegaly and Cushing's disease.

The Congress included 42 scientific lectures in 14 sessions and six plenary lectures focusing on areas of particular interest to neuroendocrinologists and related specialists alike. There was also a series of 16 'meet the professor' sessions during the congress to allow delegates to discuss the finer points of applied clinical neuroendocrinology with recognised global experts. New research was also a priority, with six oral communication sessions, including hot topics based on the most cutting-edge research, and 140 posters.

The investigators from a large European epidemiology study reported that the prevalence of neuroendocrine tumours (NETs) is higher than previously thought, and that the incidence over the last 30 years has increased.[1] This may be partly due to increased awareness and advances in diagnostic technologies. In addition to this study, a review of a database in Spain established in 1997 has provided usual insights into changes and advancements in acromegaly treatment patterns over the last three decades.[2] It found that, not surprisingly, the use of radiation therapy and dopamine agonists has decreased dramatically, whereas use of somatostatin analogues and pegvisomant has increased. Surgical rates have been maintained and is still the mainstay of treatment. There has been a steady improvement in patient outcomes, with disease now controlled in over 70% of patients. Continual updating of the epidemiology of NETs will improve understanding of this disease, it's causal factors, response to treatment and resistance profile, enabling the advancement of its diagnosis and treatment.

The presentation of data on the investigation and treatment of pituitary tumours played at central role at ENEA. These tumours account for around 15% of intracranial tumours. However, their investigation is often impeded by tissue availability, access to tumour sites and lack of differentiated cell lines. The genetic understanding of these tumours is limited and most of our understanding has been derived from mechanisms for pituitary trophic activity. Transgenic models have provided a better understanding of the multistep progression of pituitary growth, hyperplasia and neoplasia, and several factors that mediate tumorigenesis have been identified. This has enabled the cell directed therapeutic strategies for the treatment of these endocrine neoplasms.

The latest developments in the treatment include the advances in treatment options for acromegaly and Cushing's disease.

The management of Cushing's disease is complex, with challenges facing clinicians in its early diagnosis and in the provision of an effective treatment. Comorbidities associated with Cushing's disease include increased total cholesterol and glucose levels, as well as hypertension and weight gain. If diagnosed and treated early, long term effects from these comorbidities can be avoided. There are currently no licensed treatments for the pituitary related Cushing's disease, and clinicians rely on the use of other medications that have shown an effect in lowering cortisol levels in these patients, such as agents that inhibit steroidogenesis or the dopamine agonist bromocriptine. The somatostatin analogue pasireotide, which has a broad spectrum of receptor binding activity and is the first treatment to be developed specifically for the treatment of Cushing's disease, has shown promise in a phase III efficacy and safety study.[3]

Dopamine agonists are considered poorly effective in the treatment of acromegaly. However, a meta-analysis of fifteen studies investigating the efficacy of cabergoline found that control of acromegaly was achieved in more than a third of patients.[4] This increased to more than half of patients in those resistant to somatostatin analogues. None of the studies were randomised, placebo controlled. Another study has investigated the effectiveness of cabergoline as an add-on therapy for acromegaly patients resistant to long-acting octreotide.[5] Control of acromegaly, assessed by insulin-like growth factor -1 (IGF-1) levels, was achieved in around 40% of patients. Response was independent of prolactin levels.

Acromegaly is usually caused by a growth hormone (GH)-secreting pituitary adenoma, resulting in high circulating GH and IGF-I concentrations. Standard therapy is surgery. For patients who are not candidates for surgery, there are two licensed somatostatin analogues, lanreotide and octreotide. Symptoms of acromegaly can be controlled effectively in around 70% of patients with these drugs. However, this still leaves 30% of patients without adequate control of GH and IGF-1.

Surgery and medical therapy are the mainstays of treatment for patients with acromegaly. However, advances in molecular and immunohistochemical markers, as well as continual advances in clinical and laboratory research may further refine treatment for these patients in the next decade. Somatostatin analogues with effects towards specific somatostatin receptors are also being developed. Pasireotide is currently being investigated in patients. Pasireotide is a new somatostatin analogue with a broad spectrum of receptor binding activity. Two planned Phase III studies exploring the efficacy and safety of pasireotide LAR in acromegaly versus octreotide and in patients with acromegaly inadequately controlled with currently available somatostatin analogues, are planned. The design of these studies were presented at ENEA, and results are expected in the next few years.[6] [7]

In addition to somatostatin analogues and dopamine agonists, data was presented on the use of pegvisomant, with a particular focus on reducing the cardiovascular morbidity associated with acromegaly. One study showed that long term treatment with pegvisomant in acromegalic patients results in significant improvement in cardiac rhythm, with low incidence of adverse events.[8] Another demonstrated significant reduction in CV risk in acromegalic patients, particularly in patients with normalised IGF-1 levels.[9] Hybrid molecules, such as dopastatin, have demonstrated good in vitro data and everolimus induces anti-proliferative effects in GH-secreting pituitary tumour cells in vitro and may be beneficial to patients with invasive tumours resistant to current treatments.[10] The level of activity in this area of research promises a diversity of new drugs for acromegaly by 2020.




 


 

References


[1] Karavitaki N. Epidemiology of endocrine tumours.

[2] Webb S et al. Twelve years of the Spanish Acromegaly Registry (REA). Changes in acromegaly treatment and outcomes in Spain.

[3] Colao A et al. Pasireotide (SOM230) provides clinical benefit in patients with Cushing's disease: results from a large, 12-month, randomised-dose, double-blind , Phase III study.

[4] Pergola L et al. Efficacy of cabergoline in the treatment of acromegaly: a meta-analysis.

[5] Vilar L et al. Effectiveness of the addition of cabergoline to acromegalic patients resistant to long-term treatment with octreotide LAR.

[6] Bronstein M et al. A randomised, blinded, multicentre, Phase III study to assess the efficacy and safety of pasireotide LAR versus octreotide LAR in patients with active acromegaly.

[7] Colao A et al. Pasireotide LAR versus octreotide LAR or lanreotide Autogel in patients with inadequately controlled acromegaly: A Phase III, multicentre, randomised, parallel-group study.

[8] Auriemma R et al. Effects of short (6 months) and long (18 months) term treatment  with gh-receptor antagonist pegvisomant (peg) on rhythm disturbances in acromegaly.

[9]Berg C et al. Cardiovascular risk factors in treatment-resistant, active  and long-term acromegaly: comparison to matched data from the general population and the effect of disease control.

[10] Gadelha M. Management of acromegaly in 2020.