Clinical Trial: Dose Escalation of Octreotide-LAR as First-Line Therapy in Resistant Acromegaly

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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.


Detailed Summary:

This is an analytical, interventional, 24-month, open, prospective study to investigate the effect of progressive increase of octreotide-LAR doses in newly diagnosed patients with acromegaly. Primary outcome measures were GH and IGF-I control and tumor shrinkage; secondary outcome measure was glucose tolerance.

At diagnosis and every six months, 24-48 hours before changes in treatment doses was applied, were measured:

  1. Serum IGF-I levels twice in a single sample at the time 0 of the GH profile; GH levels calculated as the mean value of 3-6 samples drawn every 30 min; the average value was considered for the statistical analysis;
  2. Tumor volume on MRI studies performed on clinical 1T and 1.5T scanners, using T1 weighted gradient recalled-echo in the sagittal and coronal planes, as already reported (15,21,22). The acquisitions were repeated before and after the administration of 0.1 mmoles of gadolinium chelate (diethylene-triamine pentacetate). In all patients MRI was performed at diagnosis and after 6, 12, and 24 months of treatment. The maximal sagittal, axial and coronal diameters were measured, then tumor volume was calculated by the De Chiro and Nelson formula [(volume= sagittal*coronal*axial diameters)*π/6]. According with previous studies (13,21) on post-treatment MRI, tumor shrinkage was assessed as percent decrease of tumor volume compared with baseline.
  3. Glucose tolerance by assaying glucose and insulin levels at fasting. Only at diagnosis glucose and insulin were also measured every 30 minutes for 2 hours after the oral administration of 75 g of glucose diluted in 250 ml of saline solution. In four patients the glucose load was not performed because of overt diabetes (fasting glucose was above 7 mmol/L at two co
    Sponsor: Federico II University

    Current Primary Outcome:

    • GH and IGF-I control
    • tumor shrinkage


    Original Primary Outcome: Same as current

    Current Secondary Outcome: Glucose tolerance.

    Original Secondary Outcome: Same as current

    Information By: Federico II University

    Dates:
    Date Received: April 13, 2007
    Date Started: January 1995
    Date Completion:
    Last Updated: April 13, 2007
    Last Verified: April 2007