Octreotide as Primary Therapy for Acromegaly

Abstract

The effects of octreotide (up to 5 yr) as primary treatment in 26 patients with acromegaly were compared with those in 81 patients with acromegaly who received octreotide as secondary or adjunctive therapy after previous surgery and/or pituitary radiation. These patients were part 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 phase, patients were randomized to treatment with either 100 or 250 micrograms octreotide, sc, every 8 h for 6 months. Octreotide was then discontinued for 1 month and reinitiated at the lower dose for a total mean treatment duration of 39 months. The dose was titrated by each investigator to improve each patient's individual response, which included improvement 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 either 100 or 250 micrograms octreotide, three times daily, mean integrated GH and IGF-I concentrations after 3 and 6 months were equivalent in the primary and secondary treatment groups. During long term open label treatment, mean GH fell from 32.7 +/- 5.2 to 6.0 +/- 1.7 micrograms/L 2 h after octreotide injection in the primary therapy group and remained suppressed for a mean period of 24 months (range, 3-60 months). The mean final daily dose was 777 micrograms. In the patients receiving secondary treatment, mean GH fell from 30.2 +/- 7.6 to 5.6 +/- 1.1 micrograms/L after 3 months and remained suppressed for the remainder of the study (average dose, 635 micrograms 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 (secondary treatment group) to a mean of 2.2 +/- 0.3 x 10(3) U/L in both groups after 3 months of open label treatment and remained suppressed. IGF-I was reduced into the normal range during at least half of the study visits 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 significant difference in the percentage of responders in the primary and secondary treatment groups (70% vs. 61%), nor was there a statistical difference in the mean GH concentrations between the groups. Symptoms of headache, increased perspiration, fatigue, and joint pain were reported at baseline by 46%, 73%, 69%, and 85%, respectively, of patients in the primary therapy group and improved during 3 yr of octreotide treatment in 50-100%. Similarly, these acromegaly-related symptoms were reported by 62%, 58%, 78%, and 60% of patients in the secondary therapy group, and improvement was noted in 62-88%. Pituitary magnetic resonance imaging scans were available in 13 of 26 patients in the primary treatment group before and after 6 months of octreotide treatment. Tumor shrinkage was obser...

AcroBel – the Belgian registry on acromegaly: a survey of the ‘real-life’ outcome in 418 acromegalic subjects

“…Following reports that octreotide was equally effective in primary and adjuvant therapy (28,29) and considering the disappointing results of surgery in macroadenomas and invasive adenomas, primary medical therapy with SSA has recently been advocated as a first-line therapeutic choice for acromegalic patients not amenable to surgical cure (30). However, only 24% of 74 patients on primary medical therapy fulfilled both criteria of control versus 42% of 121 patients on secondary medical therapy.…”

Gross total resection or debulking of pituitary adenomas improves hormonal control of acromegaly by somatostatin analogs

“…As long-term treatment by SSAs permits the normalization of GH and IGF-I in a substantial Table 2 Individual GH and IGF-1 values for all patients at the four study time points. number of cases (40 -60%) (12), some physicians may opt to treat patients suffering from extrasellar macroadenomas with SSAs when compression of adjoining structures is not present (12)(13)(14)(15)(16)(17). Whether or not surgery improves the outcome of medical therapy with SSAs has not been studied previously.…”

“…Whether or not surgery improves the outcome of medical therapy with SSAs has not been studied previously. In studies of octreotide as primary treatment compared with patients who had undergone pituitary surgery or irradiation and who were receiving octreotide as second-line treatment, octreotide was equally effective (14). We hypothesized that by reducing tumor mass and decreasing basal GH secretion, the subsequent control of GH and IGF-I levels with SSAs could be improved.…”

Preclinical and clinical experiences with the role of somatostatin receptors in the treatment of pituitary adenomas

“…Therefore, several studies were initiated in which newly diagnosed patients were treated with somatostatin analogs. To date, efficacy numbers have been reported for normalizing GH (43-79%) and IGF-I (53-68%), which are comparable with efficacy numbers for adjuvant SRIF analog therapy (9)(10)(11)(12)(13)(14)(15).…”