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Long-Term Effects of Depot Long-Acting Somatostatin Analog Octreotide on Hormone Levels and Tumor Mass in Acromegaly¹

Departments of Molecular and Clinical Endocrinology and Oncology (A.C., D.F., P.M., G.L.), Neurosurgery (P.C.), and Neuroradiology (S.C.), "Federico II" University of Naples, 80131 Naples, Italy; and Novartis Pharmaceutics (V.B., I.L.), 4002 Basel, Switzerland

Address correspondence and requests for reprints to: Annamaria Colao, M.D., Department of Molecular and Clinical Endocrinology and Oncology, "Federico II" University of Naples, via S. Pansini 5, 80131 Naples, Italy. E-mail: colao{at}unina.it

Abstract

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 ± 5.6 µg/L; insulin-like growth factor I (IGF-I), 784.5 ± 40.4 µg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery.

Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12–24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (2.5 µg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 ± 0.6 vs. 2.2 ± 0.6 µg/L) and IGF-I (323.1 ± 34.9 vs. 275.5 ± 33.0 µg/L), percent suppression of GH (92.7 ± 2.0 vs. 85.9 ± 3.3%) and IGF-I (57.4 ± 4.9 vs. 61.5 ± 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients.

In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.

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