Beneficial Effect of Dose Escalation of Octreotide-LAR as First-Line Therapy in Patients With Resistant Acromegaly

Detailed Summary

Epidemiological data indicate that patients with active acromegaly have reduced life expectancy because of cardiovascular (60%) and respiratory diseases (25%) mainly (1-10). A post-treatment GH value \<5 mU/liter (equal to \<2.5 μg/liter) and IGF-I in the normal range for age are recognized as the most predictive survival indices. Since their introduction into clinical use approximately two decades ago, somatostatin analogs have been considered a cornerstone of medical therapy for acromegaly. After 12 months of treatment with octreotide-LAR, control of GH and IGF-I excess, is achieved in 54% and 63% of unselected patients (11). The proportion of subjects achieving IGF-I normalization increases significantly with time (12). Significant tumor shrinkage has also been reported in a number of studies (13,14): an average 50% tumor decrease is achieved when the drug is used exclusively, or before surgery or radiotherapy (14). In 99 unselected newly diagnosed patients after 12 months of treatment with somatostatin analogues we reported control of GH levels in 57.6% and IGF-I levels in 45.5% and a greater than 50% tumor shrinkage in 44.4% (15). The dose of LAR in different studies ranged from 10-40 mg every 28 days (q28d): high doses are generally administered in patients who do not control GH and IGF-I excess with lower doses. As reported in the meta-analysis (11) the rate of IGF-I normalization tended to be lower as octreotide-LAR dose was raised: 90% in patients treated with 10 mg, 61% with 20 mg and 53% with 30 mg. However, some further benefit by increasing the dose of octreotide-LAR was reported in some studies (16-18). Data on dose escalation of octreotide-LAR given as first-line therapy in newly diagnosed patients with acromegaly are lacking.

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