A prospective, multicentre study to investigate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of patients with acromegaly

Moises Mercado, Fatima Borges, Hakim Bouterfa, Tien-Chun Chang, Alberto Chervin, Andrew J Farrall, Attila Patocs, Stephan Petersenn, Jan Podoba, Mitra Safari, Joanna Wardlaw, SMS995B2401 Study Group, Moises Mercado, Fatima Borges, Hakim Bouterfa, Tien-Chun Chang, Alberto Chervin, Andrew J Farrall, Attila Patocs, Stephan Petersenn, Jan Podoba, Mitra Safari, Joanna Wardlaw, SMS995B2401 Study Group

Abstract

Objective: To evaluate the efficacy, safety and tolerability of octreotide LAR (long-acting repeatable octreotide) in the primary therapy of acromegaly.

Design and patients: Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10-30 mg every 4 weeks, and constituted the population used for this analysis.

Measurements and results: A clinically relevant reduction (i.e. to < or = 5 microg/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value (< or = 2.5 microg/l). At week 48, 16 more patients were considered partial GH responders (GH > 2.5 microg/l and < or = 5 microg/l) and 44% had reached a GH level < or = 2.5 microg/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14.7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 +/- 145 mm3 to 139 +/- 94 mm3 after 24 weeks and to 99 +/- 70 mm3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 +/- 5077 mm3 at baseline and 2723 +/- 3435 and 2406 +/- 3207 mm3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant (> 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period.

Conclusion: Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.

Figures

Fig. 1
Fig. 1
Mean GH values in each individual patient at baseline, and after 24 and 48 weeks of treatment with octreotide LAR. Shaded area represents a GH level

Fig. 2

Individual IGF-1 levels at baseline…

Fig. 2

Individual IGF-1 levels at baseline and after 24 and 48 weeks of treatment…

Fig. 2
Individual IGF-1 levels at baseline and after 24 and 48 weeks of treatment with octreotide LAR. Shaded areas represent the normal, age-adjusted range.

Fig. 3

Coronal MR images in a…

Fig. 3

Coronal MR images in a patient with macroadenoma (a) at baseline (volume 22…

Fig. 3
Coronal MR images in a patient with macroadenoma (a) at baseline (volume 22 702 mm3), (b) after 24 weeks (volume 15 285 mm3) and (c) after 48 weeks (volume 11 746 mm3) of treatment with octreotide LAR.

Fig. 4

Percentages in tumour volume reduction…

Fig. 4

Percentages in tumour volume reduction in micro- and macroadenomas throughout the study.

Fig. 4
Percentages in tumour volume reduction in micro- and macroadenomas throughout the study.
Fig. 2
Fig. 2
Individual IGF-1 levels at baseline and after 24 and 48 weeks of treatment with octreotide LAR. Shaded areas represent the normal, age-adjusted range.
Fig. 3
Fig. 3
Coronal MR images in a patient with macroadenoma (a) at baseline (volume 22 702 mm3), (b) after 24 weeks (volume 15 285 mm3) and (c) after 48 weeks (volume 11 746 mm3) of treatment with octreotide LAR.
Fig. 4
Fig. 4
Percentages in tumour volume reduction in micro- and macroadenomas throughout the study.

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