The AACE guidelines (PDF 93KB) note that major progress has been made in developing pharmacologic agents for acromegaly, which has facilitated more aggressive management of the disease1. They then review the major classes of pharmacologic therapy available today.
Somatostatin Analogues
Somatostatin analogues, derived from the naturally occurring inhibitory hormone somatostatin, represent a physiologically based approach to managing acromegaly. These analogues act at the site of the tumor to control GH hypersecretion. The guidelines conclude that somatostatin analogues are first-line therapy when medical treatment of acromegaly is required.
Sandostatin® (octreotide acetate) Injection is a somatostatin analogue that has been FDA-approved for the treatment of acromegaly since 1988. Sandostatin® LAR Depot (octreotide acetate for injectable suspension) the long-acting formulation of octreotide acetate, has been approved for use since 1998. Sandostatin® LAR Depot controls both GH and IGF-1 levels in up to 68% of patients and is also the only somatostatin analogue proven to shrink tumors in acromegaly1-3.
Dopamine Agonists
Dopamine agonists such as bromocriptine or cabergoline bind pituitary dopamine-2 (D2) receptors and suppress GH secretion in some patients4. One study suggests that with the newer agent, cabergoline, IGF-1 control can be achieved in about 1/3 of patients1. Clinical response to dopamine agonist therapy varies, with prolactin-secreting tumors showing a more favorable response. The AACE guidelines conclude that dopamine agonists are far less effective than somatostatin analogues or GH receptor antagonists. They may be most useful in patients with acromegaly and hyperprolactinemia, or in those with relatively minimal elevations of IGF-11.
GH Receptor Antagonists
The GH receptor antagonist pegvisomant blocks GH action peripherally by competing with the natural GH molecule for binding at the GH receptor1. Normalized IGF-1 is achieved in more than 80% of patients5. The guidelines conclude that pegvisomant should be used in patients for whom surgical treatment, somatostatin analogues, and dopamine agonists have proved ineffective or for those who are intolerant to somatostatin analogues or for those who have extremely high IGF-1 levels (>900 ng/mL), however, pegvisomant does not decrease levels of GH or have any direct effect on tumor mass1.
Learn about radiation therapy for acromegaly
Important Safety Information
Carcinoid Syndrome:
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and for the long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (62%), gastrointestinal disorders (14% to 38%), and injection-site pain (20% to 50%). Hypoglycemia (4%), hyperglycemia (27%), sinus bradycardia (19%), conduction abnormalities (9%), and arrhythmias (3%) have been reported.
The controlled clinical trials that support the marketing clearance for Sandostatin® LAR Depot did not include determination of effect on tumor size or rate of growth. Sandostatin® LAR Depot is not indicated for tumor shrinkage.
Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (52%), gastrointestinal disorders (7% to 36%), and injection-site pain (2% to 11%). Hypoglycemia (2%), hyperglycemia (15%), and hypothyroidism (2%) have been reported. While not measured in acromegalic patients receiving Sandostatin® LAR Depot, ECG changes have been reported in patients receiving immediate release Sandostatin® Injection; the degree to which these abnormalities are related to octreotide acetate is not clear, as many acromegalics have cardiovascular disease. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
