Efficacy and Acceptability of Lanreotide Autogel^® 120 mg at Different Dose Intervals in Patients with Acromegaly Previously Treated with Octreotide LAR

Abstract

Objective: To assess the efficacy of different dosing intervals of lanreotide, Somatuline Autogel^® (Lan-ATG) 120 mg in patients with acromegaly, previously treated with octreotide, long-acting release (Oct-LAR).

Patients and study design: Patients previously on Oct-LAR 10, 20, or 30 mg were switched to 6 repeated deep subcutaneous injections of Lan-ATG 120 mg at intervals of 56, 42, or 28 days, respectively. After the third injection, dose intervals were adjusted on the basis of insulin-like growth factor 1 (IGF-1) levels.

Results: The ITT (Intention To Treat) population comprised 35 patients who received at least one dose of study medication and at least one post-baseline efficacy assessment. Overall, 62.9% (n=22) of patients had normalised IGF-1 levels with Lan-ATG at study end (one injection interval after the 6^th injection of Lan-ATG), which was similar to the proportion at baseline (60.0% [n=21]). QoL did not change from baseline to study end. Patient preference for Lan-ATG was highest in the 56-day dosing interval group: 71%, 54% and 41% of the patients in the 56, 42 and 28 day groups, respectively, expressed a preference for treatment with Lan-ATG (preference for Oct-LAR: 29%, 9% and 35%, respectively, while the remainder had no preference).

Conclusion: Lan-ATG 120 mg injected at intervals of 56, 42 and 28 days provided equivalent hormonal control and QoL to Oct-LAR 10, 20 and 30 mg injected every 28 days, respectively. The proportion of patients preferring Lan-ATG treatment was greater in the longer injection interval groups.

Key words

acromegaly - lanreotide - efficacy - dose intervals

References

• 1 Antonjonijoan RM, Barbanoj MJ, Cordero JA. et al . Pharmacokinetics of a new Autogel formulation of the somatostatin analogue lanreotide after a single subcutaneous dose in healthy volunteers.  J Pharm Pharmacol. 2004;  56 471-476
• 2 Attanasio R, Baldelli R, Pivonello R. et al . Lanreotide 60 mg, a new long-acting formulation: effectiveness in the chronic treatment of acromegaly.  J Clin Endocrinol Metab. 2003;  88 5258-5265
• 3 Attanasio R, Lanzi R, Losa M. et al . Effects of lanreotide Autogel on growth hormone, insulin like growth factor 1, and tumor size in acromegaly: a 1-year prospective multicenter study.  Endocr Pract. 2008;  14 846-855
• 4 Baldelli R, Colao A, Razzore P. et al . 2-year follow-up of acromegalic patients treated with slow release lanreotide (30 mg).  J Clin Endocrinol Metab. 2000;  85 4099-4103
• 5 Barbanoj M, Antonijoan R, Morte A. et al . Pharmacokinetics of the somatostatin analog lanreotide in patients with severe chronic renal insufficiency.  Clin Pharmacol Therapeut. 1999;  66 485-491
• 6 Bronstein M, Musolino N, Jallad R. et al . Pharmacokinetic profile of lanreotide Autogel in patients with acromegaly after 4 deep subcutaneous injections of 60, 90 or 120 mg every 28 days.  Clin Endocrinol. 2005;  63 514-519
• 7 Caron P, Morange-Ramos I, Cogne M. et al . 3 year follow-up of acromegalic patients treated with intramuscular slow-release lanreotide.  J Clin Endocrinol Metab. 1997;  82 18-22
• 8 Caron PH, Beckers A, Cullen DR. et al . Efficacy of the new long-acting formulation of lanreotide autogel (Lanreotide Autogel) in the management of acromegaly.  J Clin Endocrinol Metab. 2002;  87 99-104
• 9 Caron P, Bex M, Cullen DR. et al . Group for Lanreotide Autogel Long-Term Study on Acromegaly. One-year follow-up of patients with acromegaly treated with fixed or titrated doses of lanreotide Autogel.  Clin Endocrinol (Oxf). 2004;  60 734-740
• 10 Caron P, Cogne M, Raingeard I. et al . Effectiveness and tolerability of 3-year lanreotide Autogel^® treatment in patients with acromegaly.  Clin Endocrinol. 2006;  64 209-214
• 11 Cendros J, Peraire C, Trocoñiz I. et al . Pharmacokinetics and population pharmacodynamic analysis of lanreotide Autogel.  Metabolism. 2005;  54 1276-1278
• 12 Chanson P, Salenave S. Acromegaly.  Orphanet J Rare Dis. 2008;  3 17
• 13 Chanson P, Borson-Chazot F, Kuhn J-M. et al . Lanreotide Acromegaly Study Group. Control of IGF-1 levels with titrated dosing of lanreotide Autogel over 48 weeks in patients with acromegaly.  Clin Endocrinol. 2008;  69 299-305
• 14 Croxtall JD, Scott LJ. Lanreotide Autogel^®. A review of its use in the management of acromegaly.  Drugs. 2008;  68 711-723
• 15 Elmlinger M, Kühnel W, Weber M. et al . Reference ranges for automated chemiluminescent assays for serum insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3).  Clin Chem Lab Med. 2004;  42 654-664
• 16 Freda PU, Katznelson L, van der Lely AJ. et al . Long-acting somatostatin analog therapy of acromegaly: a meta-analysis.  J Clin Endocrinol Metab. 2005;  90 4465-4473
• 17 Giustina A, Chanson P, Bronstein MD. et al . A Consensus on Criteria for Cure of Acromegaly.  J Clin Endocrinol Metab. 2010;  95 (7) 3141-3148
• 18 Holdaway IM, Rajasoorya C. Epidemiology of acromegaly.  Pituitary. 1999;  2 29-41
• 19 Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly.  J Clin Endocrinol Metab. 2004;  89 667-674
• 20 Johnson MR, Chowdrey HS, Thomas F. et al . Pharmacokinetics and efficacy of the long-acting somatostatin analogue somatuline in acromegaly.  Eur J Endocrinol. 1994;  130 229-234
• 21 Kauppinen-Makelin R, Sane T, Reunanen A. et al . A nationwide survey of mortality in acromegaly.  J Clin Endocrinol Metab. 2005;  90 4081-4086
• 22 Lucas T, Astorga R. The Spanish-Portuguese MultiCentre Autogel Study Group on Acromegaly. Efficacy of lanreotide Autogel administered every 4-8 weeks in patients with acromegaly previously responsive to lanreotide microparticles 30 mg: a phase III trial.  Clin Endocrinol. 2006;  65 320-326
• 23 Maiza JC, Vezzosi D, Matta M. et al . Long-term (up to 18 years) effects on GH/IGF-1 hypersecretion and tumour size of primary somatostatin analogue (SSTa) therapy in patients with GH-secreting pituitary adenoma responsive to SSTa.  Clin Endocrinol. 2007;  67 282-289
• 24 Melmed S. Acromegaly.  New Engl J Med. 2006;  355 2558-2573
• 25 Melmed S, Colao A, Barkan A. et al . Acromegaly Consensus Group. Guidelines for acromegaly management: An update.  J Clin Endocrinol Metab. 2009;  94 1509-1517
• 26 Melmed S, Cook D, Schopohl J. et al . Rapid and sustained reduction of serum growth hormone and insulin-like growth factor-1 in patients with acromegaly receiving lanreotide Autogel^® therapy: a randomized, placebo-controlled, multicenter study with a 52 week open extension.  Pituitary. 2010;  13 18-28
• 27 Mercado M, Borges F, Bouterfa H. et al . SMS995B2401 Study Group. 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.  Clin Endocrinol. 2007;  66 859-868
• 28 Murray RD, Melmed S. A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly.  J Clin Endocrinol Metab. 2008;  93 2957-2968
• 29 Mykytuyk M, Khyzhnyak O, Karachentsev Y. Treatment of active acromegaly with the somatostatin analogue lanreotide SR.  Endocrine Abstracts. 2009;  20 222
• 30 Nomikos P, Buchfelder M, Fahlbusch R. The outcome of surgery in 668 patients with acromegaly using current criteria of biochemical ‘cure’.  Eur J Endocrinol. 2005;  152 379-387
• 31 Ronchi CL, Boschetti M, Degli Uberti EC. et al . Italian Multicenter Autogel Study Group in Acromegaly. Efficacy of a slow release formulation of lanreotide (Autogel^® 120 mg) in patients with acromegaly previously treated with octreotide long acting release (LAR): an open, multicentre longitudinal study.  Clin Endocrinol. 2007;  67 512-519
• 32 Trocóniz IF, Cendrós JM, Peraire C. et al . Population pharmacokinetic analysis of lanreotide Autogel^® in healthy subjects. Evidence for injection interval of up to 2 months.  Clin Pharmacokinet. 2009;  48 51-62
• 33 Webb SM, Prieto L, Badia X. et al . Acromegaly quality of life questionnaire (ACROQOL). A new health-related quality of life questionnaire for patients with acromegaly: development and psychometric properties.  Clin Endocrinol. 2002;  57 251-258
• 34 Verhelst JA, Pedroncelli AM, Abs R. et al . Slow-release lanreotide in the treatment of acromegaly: a study in 66 patients.  Eur J Endocrinol. 2000;  143 577-584

1 >2.0 ng/ml was the value specified in the study protocol but more recently, a cut off value of >0.4 ng/ml has been defined ([Giustina et al. 2010]).

Correspondence