Sandostatin LAR in acromegaly: a 6-week injection interval suppresses GH secretion as effectively as a 4-week interval.

Abstract

Depot preparations of long-acting somatostatin analogues are being used increasingly in the treatment of GH hypersecretion in patients with acromegaly, either as primary treatment or as secondary treatment following incomplete surgery. In 60% of these patients, Sandostatin long-acting release (LAR), the depot preparation of octreotide, achieves effective suppression of serum GH (< 5 mU/l) and IGF-I levels. The advice is to administer Sandostatin LAR at 4-week intervals. After injection, serum octreotide shows an initial peak and thereafter maximal values between 14 and 42 days. There have been suggestions that the dose interval of this preparation could be increased, resulting in reduced costs, although this concept has not been confirmed by studies. We performed a prospective, cohort study in patients with active acromegaly but with normal serum GH and IGF-I levels during Sandostatin LAR treatment to assess whether the dose interval could be safely increased from 4 to 6 weeks, without significant effect on serum GH concentrations or other biochemical and clinical markers of GH hypersecretion. Fourteen patients (seven males) with GH concentrations below 5 mU/l during Sandostatin LAR treatment entered an 8-week withdrawal study following an injection. Subsequently, during an interval study patients received injections at 6-week intervals (t = 0, 8, 14, 20, 26, 32, 38 and 44 weeks). Study parameters (fasting GH, average GH of eight plasma samples, IGF-I, and octreotide concentrations, symptoms score and quality-of-life score) were assessed 2, 4, 6 and 8 weeks following the first injection (withdrawal) and at 26 and 44 weeks (interval study) before the next injection. During the withdrawal study, mean serum GH concentration increased significantly from 1.68 +/- 0.3 at 4 weeks to 2.57 +/- 0.5 mU/l at 6 weeks (P = 0.04, 4 vs. 6 weeks) and to 2.89 +/- 0.4 mU/l at 8 weeks (P < 0.001, 4 vs. 8 weeks). Mean serum GH concentration was below 5 mU/l in all patients at all time points, except for one patient at 8 weeks, and IGF-I levels remained normal in all patients. During withdrawal up to 8 weeks there was no significant change in serum IGF-I concentration, symptoms score or quality-of-life score. Mean serum octreotide decreased significantly from 1610 +/- 355 ng/l at 2 weeks to 1045 +/- 272 ng/l at 6 weeks (P = 0.002, 2 and 4 vs. 6 weeks) and to 559 +/- 147 ng/l at 8 weeks. In the interval study, one patient had mean serum GH above 5 mU/l associated with an increase in symptoms at 26 weeks and she was withdrawn from the study. The remaining 13 patients completed the 6-weekly injection study protocol and in the long term no significant changes in mean serum GH concentration, IGF-I concentration or symptom scores were observed (6 vs. 26 and 44 weeks). All patients had a mean serum GH concentration < 5 mU/l and serum IGF-I remained normal in 11 out of 14 patients at 26 weeks and nine out of 13 patients at 44 weeks. Moreover, the mean octreotide concentrations measured 6 weeks after a Sandostatin LAR injection did not decrease in the long term. On the basis of serum GH concentrations, most patients with serum GH levels < 5 mU/l during Sandostatin LAR treatment using a 4-weekly schedule can be effectively treated with 6-weekly injections. However, during long-term treatment with 6-weekly injections, discordant IGF-I and GH results were observed in 30% of the patients and careful clinical monitoring is therefore required.