Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review

Abstract

Acromegaly is a rare disease with a multifaceted clinical presentation. In 90-95% of patients with acromegaly, the disease is caused by a growth hormone (GH)-secreting pituitary adenoma with elevated GH levels that ultimately induce excessive hepatic secretion of insulin-like growth factor-1 (IGF-1). Somatostatin receptor ligands (SRLs) are considered the standard medical choice for the treatment of acromegaly, and normalization of GH and IGF-1 is attainable with effective therapy. This review aims to summarize the literature relative to SRL dose escalation therapy in patients with acromegaly. A United States National Library of Medicine PubMed search of SRL's was conducted using the following search terms: ((((LAR) OR ATG) OR octreotide) OR lanreotide Autogel) AND acromegaly. Related articles in non peer-reviewed journals were excluded. The rationale and benefits of SRL dose optimization therapy were investigated with emphasis on describing the clinical recognition, treatment, and management of patients with acromegaly. We found that dose escalation could provide additional biochemical control of acromegaly in patients who are inadequately controlled with conventional starting doses of octreotide LAR and lanreotide Autogel(®). Furthermore, patients should routinely have their GH and IGF-1 levels closely monitored and their SRL dose increased or decreased thereafter according to individual response.

Fig. 1

Interpretation of GH and IGF-1 levels in acromegaly. © 2010, The Endocrine Society, reproduced with permission. Giustina et al. [12]. GHRA growth hormone receptor antagonist, OGTT oral glucose tolerance test, DR discretionary recommendation, SR strong recommendation

Fig. 2

The management strategy for the treatment of acromegaly. Disease control is defined as attaining the GH and IGF-1 levels outlined in the text. First level, surgery or medical therapy (SRL); second level, SRL therapy, dose adjustment, and monitor disease progression; third level, MRI; fourth level, radiation or pegvisomant therapy; fifth level, monitor disease progression or return patient to surgery. © 2009, The Endocrine Society, reproduced with permission. Melmed et al. [10]

Fig. 3

Percent reduction of GH and IGF-1 concentrations at 12 months in patients with acromegaly treated with titrated versus fixed doses of lanreotide ATG

Fig. 4

Increase in the proportion of octreotide LAR patients with control of GH and IGF-1 after dose optimization therapy. Group A represents patients that were started and remained on the 20 mg/month dose. Group B represents patients whose starting dose was increased to 30 mg/month. Group C represents patients whose dose was increased further to 40 mg/month

Fig. 5

Percent tumor volume reduction from baseline to 12 months of treatment (12), from 12 to 24 months of treatment (24) and total tumor shrinkage (from baseline to 24 months of treatment) in patients with acromegaly. Group A represents patients that were started and remained on the 20 mg/month dose. Group B represents patients whose starting dose was increased to 30 mg/month. Group C represents patients whose dose was increased further to 40 mg/month. © 2007, The European Society of Endocrinology, reproduced with permission. Colao et al. [51]. *P < 0.01 versus same time Group A; **P < 0.01 versus same time Group A and B

Fig. 6

Patient IGF-1 levels at baseline (T0) and week 24 (T2) in patients receiving either high-frequency octreotide therapy (HF; 30 mg every 21 days) or high-dose octreotide (HD; 60 mg every 28 days) therapy. Shaded area indicates normal IGF-1 concentration range for age. © 2009, The European Society of Endocrinology, reproduced with permission. Giustina et al. [56]