Vol 70, No 4 (2019)
Original paper
Published online: 2019-06-18

open access

Page views 2461
Article views/downloads 1756
Get Citation

Connect on Social Media

Connect on Social Media

Efficacy and safety of high-dose long-acting repeatable octreotide as monotherapy or in combination with pegvisomant or cabergoline in patients with acromegaly not adequately controlled by conventional regimens: results of an open-label, multicentre study

Annamaria Colao1, Wojciech Zgliczyński2, Jan Komorowski3, Beata Kos-Kudła4, Antoine Tabarin5, Veronique Kerlan6, Francesco M. Minuto7, Carla Scaroni8, Marek Bolanowski9
Pubmed: 31274183
Endokrynol Pol 2019;70(4):305-312.

Abstract

Introduction: Long-acting repeatable (LAR) octreotide i.m. is a potent, synthetic somatostatin analogue (SSA) that requires less frequent dosing and offers quality of life (QoL) benefits in acromegaly patients compared to its shorter-acting predecessor. This study investigated the efficacy and safety of high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline in acromegalic patients with pituitary adenomas following previous failure of conventional SSA treatment.

Material and methods: After three months of high-dose Sandostatin® LAR® monotherapy (40 mg), patients who achieved biochemical control (n = 7) continued to receive the same treatment for an additional four months, whereas uncontrolled patients were randomised to receive high-dose Sandostatin® LAR® in combination with pegvisomant (n = 31) or cabergoline (n = 32). Outcomes included biochemical response at eight months, QoL, and safety.

Results: After three months, 3 of 68 (4.4%) evaluable patients achieved a biochemical control (BC) as assessed by levels of growth hormone and insulin-like growth factor-1. At eight months, 4 of 67 (6.0%) patients achieved BC, including one receiving monotherapy and three receiving Sandostatin® LAR® plus cabergoline. Partial response rate, improvements in acromegaly signs and symptoms, and changes in QoL were similar for all three groups. All treatments were well tolerated with a slight excess of adverse events in the combination arms. There were no deaths or serious adverse events leading to treatment discontinuation.

Conclusion: These data demonstrate that high-dose Sandostatin® LAR® as monotherapy or in combination with pegvisomant or cabergoline is a feasible salvage option in patients with pituitary adenomas not adequately controlled on conventional SSA regimens.

Article available in PDF format

View PDF Download PDF file

References

  1. Katznelson L, Laws ER, Melmed S, et al. Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(11): 3933–3951.
  2. Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis. 2008; 3: 17.
  3. Melmed S. Acromegaly pathogenesis and treatment. J Clin Invest. 2009; 119(11): 3189–3202.
  4. Melmed S, Casanueva FF, Klibanski A, et al. A consensus on the diagnosis and treatment of acromegaly complications. Pituitary. 2013; 16(3): 294–302.
  5. Bolanowski M, Ruchała M, Zgliczyński W, et al. Diagnostics and treatment of acromegaly — updated recommendations of the Polish Society of Endocrinology. Endokrynol Pol. 2019; 70(1): 2–18.
  6. Fleseriu M. Clinical efficacy and safety results for dose escalation of somatostatin receptor ligands in patients with acromegaly: a literature review. Pituitary. 2011; 14(2): 184–193.
  7. Melmed S, Bronstein MD, Chanson P, et al. A Consensus Statement on acromegaly therapeutic outcomes. Nat Rev Endocrinol. 2018; 14(9): 552–561.
  8. Colao A, Auriemma RS, Lombardi G, et al. Resistance to somatostatin analogs in acromegaly. Endocr Rev. 2011; 32(2): 247–271.
  9. Colao A, Lombardi G. Growth-hormone and prolactin excess. Lancet. 1998; 352(9138): 1455–1461.
  10. Lim DS, Fleseriu M. The role of combination medical therapy in the treatment of acromegaly. Pituitary. 2017; 20(1): 136–148.
  11. Anthony L, Freda PU. From somatostatin to octreotide LAR: evolution of a somatostatin analogue. Curr Med Res Opin. 2009; 25(12): 2989–2999.
  12. Paragliola RM, Corsello SM, Salvatori R. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance. Pituitary. 2017; 20(1): 109–115.
  13. Badia X, Webb SM, Prieto L, et al. Acromegaly Quality of Life Questionnaire (AcroQoL). Health Qual Life Outcomes. 2004; 2: 13.
  14. Giustina A, Bonadonna S, Bugari G, et al. High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol. 2009; 161(2): 331–338.
  15. 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.
  16. Trainer PJ, Drake WM, Katznelson L. Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med. 2000; 342(16): 1171–1177.
  17. Schreiber I, Buchfelder M, Droste M, et al. German Pegvisomant Investigators. Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: safety and efficacy evaluation from the German Pegvisomant Observational Study. Eur J Endocrinol. 2007; 156(1): 75–82.
  18. Buchfelder M, van der Lely AJ, Biller BMK, et al. Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol. 2018; 179(6): 419–427.
  19. Sandret L, Maison P, Chanson P. Place of cabergoline in acromegaly: a meta-analysis. J Clin Endocrinol Metab. 2011; 96(5): 1327–1335.
  20. Strasburger CJ, Mattsson A, Wilton P, et al. Increasing frequency of combination medical therapy in the treatment of acromegaly with the GH receptor antagonist pegvisomant. Eur J Endocrinol. 2018; 178(4): 321–329.
  21. Gadelha MR, Bronstein MD, Brue T, et al. Pasireotide C2402 Study Group. 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.
  22. Shimon I, Adnan Z, Gorshtein A, et al. Efficacy and safety of long-acting pasireotide in patients with somatostatin-resistant acromegaly: a multicenter study. Endocrine. 2018; 62(2): 448–455.
  23. Muhammad A, van der Lely AJ, Delhanty PJD. Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study). J Clin Endocrinol Metab. 2018; 103(2): 586–595.