Acromegaly: the effect of somatostatin analogues on tumour volume shrinkage Review article
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Published:
Dec 5, 2016
Keywords:
pasireotide, lanreotide, octreotide, long-acting somatostatin analogues, tumor volume reduction, insulin-like growth factor 1, growth hormone, acromegaly, somatotroph pituitary adenoma
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Abstract
Acromegaly is a rare disease, caused by growth hormone (GH) hypersecretion and secondarily elevated insulin-like growth factor 1 (IGF-1) level. Nearly all patients with acromegaly suffer from somatotroph pituitary adenoma. The main goal of treatment is to normalise both GH and IGF-1 levels, which reduces symptoms, complications and mortality. Transsphenoidal selective adenomectomy performed by an experienced neurosurgeon is the first-line therapy. Therapy with somatostatin analogues (SSA) is used as a neoadjuvant treatment prior to surgery and in a persistent disease following the surgery. The long-acting somatostatin analogues reduce serum GH/IGF-1 levels and tumour volume. In this clinical review, mechanisms and role of 1st and 2nd generation somatostatin analogues in the treatment of patients with acromegaly are presented, with particular emphasis on the effects on somatotroph pituitary adenoma volume reduction.
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Witek P, Gutowska M. Acromegaly: the effect of somatostatin analogues on tumour volume shrinkage. OncoReview [Internet]. 2016Dec.5 [cited 2024Nov.23];6(4(24):162-8. Available from: https://journalsmededu.pl/index.php/OncoReview/article/view/494
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Copyright: © Medical Education sp. z o.o. This is an Open Access article distributed under the terms of the Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). License (https://creativecommons.org/licenses/by-nc/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Address reprint requests to: Medical Education, Marcin Kuźma (marcin.kuzma@mededu.pl)
References
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2. Bolanowski M, Ruchała M, Zgliczyński W, et al. Acromegaly – a novel view of the patient Polish proposals for diagnostic and therapeutic procedures in the light of recent reports. Endokrynol Pol 2014; 65(4): 326-331.
3. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-1 on mortality in acromegaly. Eur J Endocrinol 2008; 159(2): 89-95.
4. Abs R, Verhelst J, Maiter D, et al. Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 1998; 83(2): 374-378.
5. Pisarek H, Pawlikowski M, Kunert-Radek J, Radek M. Expression of somatostatin receptor subtypes in human pituitary adenomas – immunohistochemical studies. Endokrynol Pol 2009; 60(4): 240-251.
6. Florio T. Somatostatin/somatostatin receptor signalling: Phosphotyrosine phosphatases. Mol Cell Endocrinol 2008; 286(1-2): 40-48.
7. Theodoropoulou M, Zhang J, Laupheimer S, et al. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumour cells by altering phosphatidylinositol 3-kinase signalling and inducing Zac1 expression. Cancer Res 2006; 66(3): 1576-1582.
8. Theodoropoulou M, Tichomirowa MA, Sievers C, et al. Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly. Int J Cancer 2009; 125(9): 2122-2126.
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10. Colao A, Pivonello R, Auriemma RS, et al. Growth hormone-secreting tumour shrinkage after 3 months of octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab 2008; 93(9): 3436-3442.
11. Mercado M, Borges F, Bouterfa H, et al. 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 (Oxf ) 2007; 66(6): 859-868.
12. Colao A, Pivonello R, Auriemma RS, et al. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol 2007; 157(5): 579-587.
13. Caron PJ, Bevan JS, Petersenn S, et al. Tumour shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 2014; 99(4): 1282-1290.
14. 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(11): 5258-5265.
15. Colao A, Ferone D, Cappabianca P, et al. Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 1997; 82(10): 3308-3314.
16. Stevenaert A, Beckers A. Presurgical Octreotide: treatment in acromegaly. Metabolism 1996; 45(8 Suppl 1): 72-74.
17. Abe T, Lüdecke DK. Effects of preoperative octreotide treatment on different subtypes of 90 GH-secreting pituitary adenomas and outcome in one surgical centre. Eur J Endocrinol 2001; 145(2): 137-145.
18. Lucas T, Astorga R, Catalá M. Preoperative lanreotide treatment for GH-secreting pituitary adenomas: effect on tumour volume and predictive factors of significant tumour shrinkage. Clin Endocrinol (Oxf ) 2003; 58(4): 471-481.
19. Zieliński G, Podgórski JK, Koziarski A, et al. Preoperative administration of a slow releasing somatostatin analog (SR-lanreotide, BIM 23014) in patients with acromegaly in the course of GH-releasing adenoma. Neurol Neurochir Pol 2001; 35(3): 423-437.
20. Carlsen SM, Lund-Johansen M, Schreiner T, et al. Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial. J Clin Endocrinol Metab 2008; 93(8): 2984-2990.
21. Colao A, Attanasio R, Pivonello R, et al. Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2006; 91(1): 85-92.
22. Yetkin DO, Boysan SN, Tiryakioglu O, et al. Forty month follow-up of persistent and difficultly controlled acromegalic patients treated with depot long acting somatostatin analog octreotide. Endocr J 2007; 54(3): 459-464.
23. Colao A, Pivonello R, Auriemma RS, et al. Predictors of tumour shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 2006; 91(6): 2112-2118.
24. Ben-Shlomo A, Melmed S. Somatostatin agonists for treatment of acromegaly. Mol Cell Endocrinol 2008; 286(1-2): 192-198.
25. Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev 2011; 32(2): 247-271.
26. Petersenn S, Schopohl J, Barkan A, et al. Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. J Clin Endocrinol Metab 2010; 95(6): 2781-2789.
27. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 2014; 99(3): 791-799.
28. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol 2014; 2(11): 875-884.
2. Bolanowski M, Ruchała M, Zgliczyński W, et al. Acromegaly – a novel view of the patient Polish proposals for diagnostic and therapeutic procedures in the light of recent reports. Endokrynol Pol 2014; 65(4): 326-331.
3. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-1 on mortality in acromegaly. Eur J Endocrinol 2008; 159(2): 89-95.
4. Abs R, Verhelst J, Maiter D, et al. Cabergoline in the treatment of acromegaly: a study in 64 patients. J Clin Endocrinol Metab 1998; 83(2): 374-378.
5. Pisarek H, Pawlikowski M, Kunert-Radek J, Radek M. Expression of somatostatin receptor subtypes in human pituitary adenomas – immunohistochemical studies. Endokrynol Pol 2009; 60(4): 240-251.
6. Florio T. Somatostatin/somatostatin receptor signalling: Phosphotyrosine phosphatases. Mol Cell Endocrinol 2008; 286(1-2): 40-48.
7. Theodoropoulou M, Zhang J, Laupheimer S, et al. Octreotide, a somatostatin analogue, mediates its antiproliferative action in pituitary tumour cells by altering phosphatidylinositol 3-kinase signalling and inducing Zac1 expression. Cancer Res 2006; 66(3): 1576-1582.
8. Theodoropoulou M, Tichomirowa MA, Sievers C, et al. Tumor ZAC1 expression is associated with the response to somatostatin analog therapy in patients with acromegaly. Int J Cancer 2009; 125(9): 2122-2126.
9. Colao A, Auriemma RS, Pivonello R. The effects of somatostatin analogue therapy on pituitary tumour volume in patients with acromegaly. Pituitary 2016; 19(2): 210-221.
10. Colao A, Pivonello R, Auriemma RS, et al. Growth hormone-secreting tumour shrinkage after 3 months of octreotide-long-acting release therapy predicts the response at 12 months. J Clin Endocrinol Metab 2008; 93(9): 3436-3442.
11. Mercado M, Borges F, Bouterfa H, et al. 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 (Oxf ) 2007; 66(6): 859-868.
12. Colao A, Pivonello R, Auriemma RS, et al. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol 2007; 157(5): 579-587.
13. Caron PJ, Bevan JS, Petersenn S, et al. Tumour shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial. J Clin Endocrinol Metab 2014; 99(4): 1282-1290.
14. 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(11): 5258-5265.
15. Colao A, Ferone D, Cappabianca P, et al. Effect of octreotide pretreatment on surgical outcome in acromegaly. J Clin Endocrinol Metab 1997; 82(10): 3308-3314.
16. Stevenaert A, Beckers A. Presurgical Octreotide: treatment in acromegaly. Metabolism 1996; 45(8 Suppl 1): 72-74.
17. Abe T, Lüdecke DK. Effects of preoperative octreotide treatment on different subtypes of 90 GH-secreting pituitary adenomas and outcome in one surgical centre. Eur J Endocrinol 2001; 145(2): 137-145.
18. Lucas T, Astorga R, Catalá M. Preoperative lanreotide treatment for GH-secreting pituitary adenomas: effect on tumour volume and predictive factors of significant tumour shrinkage. Clin Endocrinol (Oxf ) 2003; 58(4): 471-481.
19. Zieliński G, Podgórski JK, Koziarski A, et al. Preoperative administration of a slow releasing somatostatin analog (SR-lanreotide, BIM 23014) in patients with acromegaly in the course of GH-releasing adenoma. Neurol Neurochir Pol 2001; 35(3): 423-437.
20. Carlsen SM, Lund-Johansen M, Schreiner T, et al. Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure short-term postoperative rates: a prospective, randomized trial. J Clin Endocrinol Metab 2008; 93(8): 2984-2990.
21. Colao A, Attanasio R, Pivonello R, et al. Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly. J Clin Endocrinol Metab 2006; 91(1): 85-92.
22. Yetkin DO, Boysan SN, Tiryakioglu O, et al. Forty month follow-up of persistent and difficultly controlled acromegalic patients treated with depot long acting somatostatin analog octreotide. Endocr J 2007; 54(3): 459-464.
23. Colao A, Pivonello R, Auriemma RS, et al. Predictors of tumour shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 2006; 91(6): 2112-2118.
24. Ben-Shlomo A, Melmed S. Somatostatin agonists for treatment of acromegaly. Mol Cell Endocrinol 2008; 286(1-2): 192-198.
25. Colao A, Auriemma RS, Lombardi G, Pivonello R. Resistance to somatostatin analogs in acromegaly. Endocr Rev 2011; 32(2): 247-271.
26. Petersenn S, Schopohl J, Barkan A, et al. Pasireotide (SOM230) demonstrates efficacy and safety in patients with acromegaly: a randomized, multicenter, phase II trial. J Clin Endocrinol Metab 2010; 95(6): 2781-2789.
27. Colao A, Bronstein MD, Freda P, et al. Pasireotide versus octreotide in acromegaly: a head-to-head superiority study. J Clin Endocrinol Metab 2014; 99(3): 791-799.
28. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide versus continued treatment with octreotide or lanreotide in patients with inadequately controlled acromegaly (PAOLA): a randomised, phase 3 trial. Lancet Diabetes Endocrinol 2014; 2(11): 875-884.