Exp Clin Endocrinol Diabetes 2005; 113(3): 139-144
DOI: 10.1055/s-2005-837520
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Four-Year Follow-Up of Acromegalic Patients Treated with the New Long-Acting Formulation of Lanreotide (Lanreotide Autogel)

B. Gutt1 , M. Bidlingmaier1 , K. Kretschmar1 , C. Dieterle1 , B. Steffin1 , J. Schopohl1
  • 1Department of Internal Medicine Innenstadt, University of Munich, Germany
Further Information

Publication History

Received: April 30, 2004 First decision: June 28, 2004

Accepted: September 9, 2004

Publication Date:
23 March 2005 (online)

Abstract

Lanreotide Autogel (Ipsen) is a long-acting somatostatin analogue (SA) in a new galenic formulation suitable for subcutaneous (s.c.) injection. In our department, 11 patients with therapy-resistant acromegaly were treated with Lanreotide Autogel for 48 months. 10/11 patients had previously undergone transsphenoidal surgery. For a median duration of 1.4 years prior to Lanreotide Autogel, the patients received Lanreotide PR 30 mg every 7, 10, or 14 days.

60, 90, or 120 mg of Lanreotide Autogel was administered by deep s.c. injection every 28 days, with the higher dosage being given to those with the previously shortest injection interval under Lanreotide PR.

Dose was adjusted on the basis of Growth Hormone (GH) level after 4, 8, and 12 months with a minimum dose of 60 mg and a maximum dose of 120 mg. The efficacy of Lanreotide Autogel treatment was evaluated by measuring GH concentrations (4 hour profiles) and IGF-I levels. Before switching to Lanreotide Autogel, the multiple of the upper limit of normal (xULN) of IGF‐I levels was 1.2 (median) and the median GH level was 1.3 µg/l. 3 out of 11 patients had an IGF-I within the age- and sex-adjusted normal range. After 48 months of treatment with Lanreotide Autogel, six patients had an IGF-I within the normal range. Median GH levels were at 1.3 µg/l and xULN of IGF-I was at 1.0 compared to Lanreotide PR 30 mg treatment (p < 0.001). At the end of the study, 8 patients received 120 mg Lanreotide Autogel, 2 patients 90 mg and 1 patient 60 mg, respectively. There was slight but significant deterioration of glucose metabolism with an increase of HbA1c.

In conclusion, the new galenic formulation of Lanreotide improves not only the control of biochemical markers of acromegaly compared to the conventional PR formulation, but is also easier to administer given its deep s.c. method of administration. Glucose metabolism has to be followed carefully in patients on high-dose Lanreotide Autogel.

References

  • 1 Baldelli R, Battista C, Leonetti F, Ghiggi M R, Ribaudo M C, Paoloni A, D'Amico E, Ferretti E, Baratta R, Liuzzi A, Trischitta V, Tamburrano G. Glucose homeostasis in acromegaly: effects of long-acting somatostatin analogues treatment.  Clin Endocrinol (Oxf). 2003;  59 492-499
  • 2 Caron P, Beckers A, Cullen D R, Goth M I, Gutt B, Laurberg P, Pico A M, Valimaki M, Zgliczynski W. Efficacy of the new long-acting formulation of lanreotide (Lanreotide Autogel) in the management of acromegaly.  J Clin Endocrinol Metab. 2002;  87 99-104
  • 3 Caron P, Bex M, Cullen D R, Feldt-Rasmussen U, Pico Alfonso A M, Pynka S, Racz K, Schopohl J, Tabarin A, Valimaki M J. One-year follow-up of patients with acromegaly treated with fixed or titrated doses of Lanreotide Autogel.  Clin Endocrinol (Oxf). 2004;  60 734-740
  • 4 Caron P, Cogne M, Gusthiot-Joudet B, Wakim S, Catus F, Bayard F. Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201 - 995).  Eur J Endocrinol. 1995;  132 320-325
  • 5 Chanson P, Boerlin V, Ajzenberg C, Bachelot Y, Benito P, Bringer J, Caron P, Charbonnel B, Cortet C, Delemer B, Escobar-Jimenez F, Foubert L, Gaztambide S, Jockenhoevel F, Kuhn J M, Leclere J, Lorcy Y, Perlemuter L, Prestele H, Roger P, Rohmer V, Santen R, Sassolas G, Scherbaum W A, Schopohl J, Torres E, Varela C, Villamil F, Webb S M. Comparison of octreotide acetate LAR and lanreotide SR in patients with acromegaly.  Clin Endocrinol (Oxf). 2000;  53 577-586
  • 6 Colao A, Ferone D, Marzullo P, Cappabianca P, Cirillo S, Boerlin V, Lancranjan I, Lombardi G. Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly.  J Clin Endocrinol Metab. 2001;  86 2779-2786
  • 7 Cozzi R, Attanasio R, Montini M, Pagani G, Lasio G, Lodrini S, Barausse M, Albizzi M, Dallabonzana D, Pedroncelli A M. Four-year treatment with octreotide long-acting repeatable in 110 acromegalic patients: predictive value of short-term results?.  J Clin Endocrinol Metab. 2003;  88 3090-3098
  • 8 Drake W M, Rowles S V, Roberts M E, Fode F K, Besser G M, Monson J P, Trainer P J. Insulin sensitivity and glucose tolerance improve in patients with acromegaly converted from depot octreotide to pegvisomant.  Eur J Endocrinol. 2003;  149 521-527
  • 9 Flogstad A K, Halse J, Bakke S, Lancranjan I, Marbach P, Bruns C, Jervell J. Sandostatin LAR in acromegalic patients: long-term treatment.  J Clin Endocrinol Metab. 1997;  82 23-28
  • 10 Freda P U. Somatostatin analogs in acromegaly.  J Clin Endocrinol Metab. 2002;  87 3013-3018
  • 11 Giustina A, Barkan A, Casanueva F F, Cavagnini F, Frohman L, Ho K, Veldhuis J, Wass J, Von Werder K, Melmed S. Criteria for cure of acromegaly: a consensus statement.  J Clin Endocrinol Metab. 2000;  85 526-529
  • 12 Grass P, Marbach P, Bruns C, Lancranjan I. Sandostatin LAR (microencapsulated octreotide acetate) in acromegaly: pharmacokinetic and pharmacodynamic relationships.  Metabolism. 1996;  45 27-30
  • 13 Ho K K, Jenkins A B, Furler S M, Borkman M, Chisholm D J. Impact of octreotide, a long-acting somatostatin analogue, on glucose tolerance and insulin sensitivity in acromegaly.  Clin Endocrinol (Oxf). 1992;  36 271-279
  • 14 Koop B L, Harris A G, Ezzat S. Effect of octreotide on glucose tolerance in acromegaly.  Eur J Endocrinol. 1994;  130 581-586
  • 15 Kuhn J M, Legrand A, Ruiz J M, Obach R, De Ronzan J, Thomas F. Pharmacokinetic and pharmacodynamic properties of a long-acting formulation of the new somatostatin analogue, lanreotide, in normal healthy volunteers.  Br J Clin Pharmacol. 1994;  38 213-219
  • 16 Lamberts S W, van der Lely A J, de Herder W W, Hofland L J. Octreotide.  N Engl J Med. 1996;  334 246-254
  • 17 Lightman S. Somatuline Autogel: an extended release lanreotide formulation.  Hosp Med. 2002;  63 162-165
  • 18 Marek J, Hana V, Krsek M, Justova V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide.  Eur J Endocrinol. 1994;  131 20-26

Dr. Bodo Gutt

Medizinische Klinik Innenstadt, Klinikum der LMU

Ziemssenstr. 1

80336 Munich

Germany

Phone: + 49(0)8951602111

Fax: + 49 (0) 89 51 60 45 66

Email: Bodo.Gutt@med.uni-muenchen.de

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