Dose Escalation of Octreotide-LAR as First-Line Therapy in Resistant Acromegaly
Status:
Completed
Trial end date:
2006-12-01
Target enrollment:
Participant gender:
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.