OCTREOTIDE AS PRIMARY THERAPY FOR ACROMEGALY

The effects of octreotide (up to 5 yr) as primary treatment in 26 pati ents with acromegaly were compared with those in 81 patients with acro megaly who received octreotide as secondary or adjunctive therapy afte r previous surgery and/or pituitary radiation. These patients were par t of a multicenter study that took place between 1989-1995. The study was divided into 3 phases beginning with a 1-month placebo-controlled treatment period followed by a 1-month washout period. In the second p hase, patients were randomized to treatment with either 100 or 250 mu g octreotide, sc, every 8 h for 6 months. Octreotide was then disconti nued for 1 month and reinitiated at the lower dose for a total mean tr eatment duration of 39 months. The dose was titrated by each investiga tor to improve each patient's individual response, which included impr ovement in symptoms and signs of acromegaly as well as reduction of GH and insulin-like growth factor I(IGF-I) into the normal range. In the second phase of the study, in which patients were randomized to eithe r 100 or 250 mu g octreotide, three times daily, mean integrated GH an d IGF-I concentrations after 3 and 6 months were equivalent in the pri mary and secondary treatment groups. During long term open label treat ment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 mu g/L 2 h after o ctreotide injection in the primary therapy group and remained suppress ed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 mu g In the patients receiving secondary treatment , mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 mu g/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 mu g daily). Mean IGF-I concentrations fell from 5.2 +/- 0.5 x 10( 3) U/L (primary treatment group) and 4.7 +/- 0.4 x 10(3) U/L (secondar y treatment group) to a mean of 2.2 +/- 0.3 x 103 U/L in both groups a fter 3 months of open label treatment and remained suppressed. IGF-I w as reduced into the normal range during at least half of the study vis its in 68% of the primary treatment group and in 62% of the secondary treatment group. Patients whose GH levels fell to at least 2 SD below the baseline mean GH were considered responders. There was no signific ant difference in the percentage of responders in the primary and seco ndary treatment groups (70% vs. 61%), nor was there a statistical diff erence in the mean GH concentrations between the groups. Symptoms of h eadache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in t he primary therapy group and improved during 3 yr of octreotide treatm ent in 50-100%. Similarly, these acromegaly-related symptoms were repo rted by 62%, 58%, 78%, and 60% of patients in the secondary therapy gr oup, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary trea tment group before and after 6 months of octreotide treatment. Tumor s hrinkage was observed in 6 of 13 patients, with reduction in tumor vol ume greater than 25% in only 3. Of 6 patients with documented tumor sh rinkage, IGF-I was reduced into the normal range in 4 patients. Of the 7 remaining patients in whom tumor shrinkage was less than 10%, IGF-I was reduced into the normal range in 5 patients. The degree of tumor shrinkage did not correlate with the percent reduction in IGF-I or GH. In summary, octreotide was equally effective in 26 previously untreat ed acromegalic patients (primary treatment group) and 81 patients prev iously treated with either surgery or pituitary radiation (secondary t reatment group). These observations call into question the current pra ctice of surgical resection of all newly diagnosed GH-secreting pituit ary adenomas regardless of the likelihood of cure. Although surgery is the treatment of choice in patients with tumors likely to be complete ly resected, our results suggest that if the possibility of surgical c ure is low, as in patients with large or invasive tumors, then octreot ide may be a reasonable primary therapeutic modality provided that the tumor does not threaten vision or neurological function.