Somatostatin receptor ligands in the treatment of acromegaly

Abstract

First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.

A Consensus Statement on acromegaly therapeutic outcomes

“…The SRLs octreotide, lanreotide and pasireotide, as well as the dopamine agonist cabergoline, bind cognate receptors in the adenoma and suppress GH secretion; the GH antagonist pegvisomant blocks GH action in the periphery and blocks generation of IGF1 (refs [57][58][59] ).…”

E‐cadherin expression is associated with somatostatin analogue response in acromegaly

“…2 However, the response to SSAs treatment is largely variable. [3][4][5] Recent prospective studies have shown success rates for SSAs (20%-40% of patients) lower than initially reported (recently reviewed in 6 ). While differences in patient selection and definitions of response to treatment may partly account for these discrepancies among published studies, there is certainly considerable variability in the efficacy of SSAs among patients in each individual study.…”

Treatment escape reduces the effectiveness of cabergoline during long‐term treatment of acromegaly in monotherapy or in association with first‐generation somatostatin receptor ligands

“…The control rates with pegvisomant are also higher, being more than 90% in clinical trials and 63% in a large databank of real‐life treatment . Therefore, the control rate we found with CAB is lower than that observed with other medical treatments in acromegaly …”

“…[28][29][30][31] Therefore, the control rate we found with CAB is lower than that observed with other medical treatments in acromegaly. 26,27,30,32 It is important to highlight that the control rate observed in our study probably overestimates the efficacy of CAB in monotherapy, as in our centre, only patients with less severe disease tend to be selected for CAB treatment in monotherapy. This potential bias was mainly due to the previous data in the literature showing that those patients with mild disease are the ones with a better chance of disease control with CAB.…”