To the content
3 . 2022

Modern realities and prospects of drug treatment of acromegaly

Abstract

The continuing curation complexity of the curation of acromegaly is due to the multiplicity of pathomorphological variants of growth hormone-secreting adenomas and the lack of a differentiated approach when choosing a treatment strategy. The review presents up-to-date data indicating the long-term effectiveness of the use of 1st and 2nd generation somatostatin analogues in patients with acromegaly as mono- or combination therapy. Clinical, laboratory, morphological and therapeutic prognostic factors have been identified that allow assessing the scenario of tumor development and increasing the effectiveness of drug therapy, taking into account the heterogeneity of somatotroph adenomas. New promising dosage forms aimed at increasing the duration of the therapeutic effect, a complex effect on various subtypes of somatostatin receptors and increasing adherence to treatment are described.

Keywords:acromegaly; drug treatment; somatostatin analogues

Funding. The study had no sponsor support.

Conflict of interest. The authors declare no conflict of interest.

For citation: Pronin V.S., Antsiferov M.B., Alexeeva T.M., Pronin E.V. Modern realities and prospects of drug treatment of acromegaly. Endokrinologiya: novosti, mneniya, obuchenie [Endocrinology: News, Opinions, Training]. 2022; 11 (3): 27–36. DOI: https://doi.org/10.33029/2304-9529-2022-11-3-27-36 (in Russian)

References

1. Kasuki L., Wildemberg L.E., Gadelha M. Management of endocrine disease: personalized medicine in the treatment of acromegaly. Eur J Endocrinol. 2018; 178 (3): R89–100. DOI: https://doi.org/10.1530/EJE-17-1006

2. Gil J., Marques-Pamies M., Sampedro M., Webb S.M., Serra G., Salinas I., et al. Data mining analyses for precision medicine in acromegaly: a proof of concept. Sci Rep. 2022; 12 (1): 8979. DOI: https://doi.org/10.1038/s41598-022-12955-2

3. Gadelha M.R., Wildemberg L.E., Kasuki L. The future of somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2022; 107 (2): 297–308. DOI: https://doi.org/10.1210/clinem/dgab726

4. Anthony L., Freda P.U. From somatostatin to octreotide LAR: evolution of a somatostatin analogue. Curr Med Res Opin. 2009; 25 (12): 2989–99. DOI: https://doi.org/10.1185/03007990903328959

5. Ӧberg K., Lamberts W.J. Somatostatin analogues in acromegaly and gastroenteropancreatic neuroendocrine tumors: past, present and future. Endocr Relat Cancer. 2016; 23: R551–66. DOI: https://doi.org/10.1530/ERC-16-0151

6. Gomes-Porras M., Cardenas-Salas J., Alvares-Escola C. Somatostatin analogs in clinical practice. A review. Int J Mol Sci. 2020; 21 (5): 1682. DOI: https://doi.org/10.3390/ijms21051682

7. Cuevas-Ramos D., Fleseriu M. Somatostatin receptor ligands and resistance to treatment in pituitary adenomas. J Mol Endocrinol. 2014; 52 (3): 223–40. DOI: https://doi.org/10.1530/JME-14-0011

8. Wolin E.M., Manon A., Chassaing C., Lewis A., Bertocchi L., Richard J., et al. Lanreotide depot: an antineoplastic treatment of carcinoid or neuroendocrine tumors. J Gastrointest Cancer. 2016; 47 (4): 366–74. DOI: https://doi.org/10.1007/s12029-016-9866-9

9. Adelman D.T., Genechten D.V., Megret C.M., Truong Thanh X-M.T., Hand P., Martin W.A. Co-creation of a lanreotide autogel/depot syringe for the treatment of acromegaly and neuroendocrine tumors through collaborative human factor studies. Adv Ther. 2019; 36: 3909–23. DOI: https://doi.org/10.1007/s12325-019-01112-3

10. Adelman D., Truong Thanh X.-M., Feuilly M., Houchard A., Cella D. Evaluation of nurse preferences between the lanreotide autogel new syringe and the octreotide long-acting release syringe: an international simulated-use study (PRESTO). Adv Ther. 2020; 37 (4): 1608–19. DOI: https://doi.org/10.1007/s12325-020-01255-8

11. Corica G., Ceraudo M., Campana C., Nista F., Cocchiara F., Boschetti V., et al. Octreotide-resistant acromegaly: challenges and solutions. Ther Clin Risk Manag. 2020; 16: 379–91. DOI: https://doi.org/10.2147/TCRM.5183360

12. Gadelha M.R., Wildemberg L.E., Bronstein M.D., Gatto F., Ferone D. Somatostatin receptor ligands in the treatment of acromegaly. Pituitary. 2017; 20 (1): 100–8. DOI: https://doi.org/10.1007/s11102-017-0791-0

13. Dreval A.V., Pokramovich Yu.G., Tishenina R.S. The effectiveness of analysis of octreotide-depo, a long-acting somatostatin analog, for the treatment of the patients presenting with active phase of acromegalia. Problemy endokrinologii [Problems of Endocrinology]. 2014; 60 (3): 10–4. DOI: https://doi.org/10.14341/probl201460310-14 (in Russian)

14. Ilovayskaya I.A. Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy. Meditsinskiy sovet [Medical Council]. 2022; 16 (10): 148–52. DOI: https://doi.org/10.21518/2079-701X-2022-16-10-148-152 (in Russian)

15. Colao A., Auriemma R.S., Pivonello R. The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly. Pituitary. 2016; 19: 210–21. DOI: https://doi.org/10.1007/s11102-015-0677-yde

16. Pichler R., Kalev O., Tomancok B., Sonnberger M., Ehrlich D., Hodolic M. Somatostatin receptor subtype expression in patients with acromegaly and complicated clinical course. Diagnostics (Basel). 2021; 11 (6): 1050. DOI: https://doi.org/10.3390/diagnostics11061050

17. Neggers S.J., Pronin V., Balcere I., Lee M.K., Rozhinskaya L., Bronstein M.D., et al. Lanreotide autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: the LEAD study. Eur J Endocrinol. 2015; 173 (3): 313–23. DOI: https://doi.org/10.1530/EJE-15-0215

18. Coopmans E.C., Korevaar T.I.M., van Meyel S.W.F., Daly A.F., Chanson P., Brue T., et al. Multivariable prediction model for biochemical response to first-generation somatostatin receptor ligands in acromegaly. J Clin Endocrinol Metab. 2020; 105 (9): dgaa387. DOI: https://doi.org/10.1210/clinem/dgaa387

19. Bolanowski M., Zgliczynski W., Sowinski J., Baldys-Waligorka A., Bednarek-Tupikowska G., Witek P., et al. Therapeutic effect of presurgical treatment with longacting octreotide (Sandostatin® LAR®) in patients with acromegaly. Endokrynol Pol. 2020; 71 (4): 285–91. DOI: https://doi.org/10.5603/EP.a2020.0050

20. Yang C., Li G., Jiang S., Bao X., Wang R. Preoperative somatostatin analogues in patients with newly-diagnosed acromegaly: a systematic review and meta-analysis of comparative studies. Sci Rep. 2019; 9: 1–9. DOI: https://doi.org/10.1038/s41598-019-50639-6

21. Caron P.J., Petersenn S., Houchard A., Sert C., Bevan J.S., Group P.S. Glucose and lipid levels with lanreotide autogel 120 mg in treatment-naïve patients with acromegaly: data from the PRIMARYS study. Clin Endocrinol (Oxf). 2017; 86 (4): 541–51. DOI: https://doi.org/10.1111/cen.13285

22. Grasso L.F.S., Auriemma R.S., Pivonello R., Colao A. Adverse events associated with somatostatin analogs in acromegaly. Expert Opin Drug Saf. 2015; 14: 1213–26. DOI: https://doi.org/10.1517/14740338.2015.1059817

23. Bolanowski M., Katuzny V., Witek P., Jawiarczyk-Przybylowska A. Pasireotide – a novel somatostatin receptor ligand after 20 years of use. Rev Endocr Metab Disord. 2022; 23 (3): 601–20. DOI: https://doi.org/10.1007/s11154-022-09710-3

24. Silverstein J.M. Hyperglycemia induced by pasireotide in patients with Cushing’s disease or acromegaly. Pituitary. 2016; 19 (5): 536–43. DOI: https://doi.org/10.1007/s11102-016-0734-1

25. Lopes M.B.S. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017; 134 (4): 521–35. DOI: https://doi.org/10.1007/s00401-017-1769-8

26. Asa S.L., Casar-Borota O., Chanson P., Delgrange E., Earls P., Ezzat S., et al. From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal. Endocr Relat Cancer. 2017; 24: C5–8. DOI: https://doi.org/10.1530/ERC-17-0004

27. Kiseljak-Vassiliades K., Carlson N.E., Borges M.T., Kleinschmidt-DeMasters B.K., Lillehei K.O., Kerr J.M., Wierman M.E. Growth hormone tumor histological subtypes predict response to surgical and medical therapy. Endocrine. 2015; 49 (1): 231–41. DOI: https://doi.org/10.1007/s12020-014-0383-y

28. Petersenn S., Houchard A., Sert C., Caron P.J., Group P.S. Predictive factors for responses to primary medical treatment with lanreotide autogel 120 mg in acromegaly: post hoc analyses from the PRIMARYS study. Pituitary. 2020; 23 (2): 171–81. DOI: https://doi.org/10.1007/s11102-019-01020-3

29. Liu W., Xie L., He M., Shen M., Zhu J., Yang Y., et al. Expression of somatostatin receptor 2 in somatotropinoma correlated with the short-term efficacy of somatostatin analogues. Int J Endocrinol. 2017; 2017: 9606985. DOI: https://doi.org/10.1155/2017/9606985

30. Sahakian N., Castinetti F., Brue T., Cuny T. Current and emerging medical therapies in pituitary tumors. J Clin Med. 2022; 11 (4): 955. DOI: https://doi.org/10.3390/jcm11040955

31. Tortora F., Negro A., Grasso L.F.S., Colao A., Pivonello R., Splendiani A., et al. Pituitary magnetic resonance imaging predictive role in the therapeutic response of growth hormone-secreting pituitary adenomas. Gland Surg. 2019; 8 (suppl 3): S150–8. DOI: https://doi.org/10.21037/gs.2019.06.04

32. Pronin E.V., Antsiferov M.B., Alekseeva T.M., Urusova L.S., Lapshina A.M., Mokrysheva N.G. Optimization of drug treatment of acromegaly (clinical and morphological comparison). Farmateka [Pharmateca]. 2022; 29 (4): 44–52 DOI: https://doi.org/10.18565/pharmateca.2022.4.44-52

33. Gadelha M.R., Bronstein M.D., Brue T., Coculescu M., Freseriu M., Guitelman M., 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: 875–84. DOI: https://doi.org/10.1016/S2213-8587(14)70169-X

34. Stelmachowska-Banas M., Czajka-Oraniec I., Tomasik A., Zgliczynski W. Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation. Pituitary. 2022; 25 (1): 180–90. DOI: https://doi.org/10.1007/s11102-021-01185-w

35. Bollerslev J., Heck A., Olarescu N.C. Management of endocrine disease: individualised management of acromegaly. Eur J Endocrinol. 2019; 181 (2): R57–71. DOI: https://doi.org/10.1530/EJE-19-0124

36. Puig-Domingo M., Soto A., Venegas E. Use of lanreotide in combination with cabergoline or pegvisomant in patients with acromegaly in the clinical practice: the ACROCOMB study. Endocrinol Nutr. 2016; 63 (8): 397–408. DOI: https://doi.org/10.1016/j.endonu.2016.05.010

37. Ghajar A., Jones P.S., Guarda F.J., Faje A., Tritos N.A., Miller K.K., et al. Biochemical control in acromegaly with multimodality therapies: outcomes from a pituitary center and changes over time. J Clin Endocrinol Metab. 2020; 105 (3): dgz187. DOI: https://doi.org/10.1210/clinem/dgz187

38. Buchfelder M., van der Lely A.J., Biller B.M.K., Webb S.M., Brue T., Strasburger C.J., et al. Long-term treatment with pegvisomant: observations from 2090 acromegaly patients in ACROSTUDY. Eur J Endocrinol. 2018; 179 (6): 419–27. DOI: https://doi.org/10.1530/EJE-18-0616

39. Neggers S.J.C.M.M., Franck S.E., de Rooij F.W., Dallenga A.H., Poublon R.M., Feelders R.A., et al. Long-term efficacy and safety of pegvisomant in combination with long-acting analogues in acromegaly. J Clin Endocrinol Metab. 2014; 99: 3644–52. DOI: https://doi.org/10.1210/jc.2014-2032

40. Franck S.E., Muhammad A., van der Lely A.J., Neggers S.J.C.M.M. Combined treatment of somatostatin analogues with pegvisomant in acromegaly. Endocrine. 2016; 52 (2): 206–13. DOI: https://doi.org/10.1007/s12020-015-0810-8

41. Samson S.L., Nachtigall L.B., Fleseriu M., Gordon M.B., Bolanowski M., Labadzhyan A., et al. Maintenance of acromegaly control in patients switching from injectable somatostatin receptor ligands to oral octreotide. Clin Endocrinol Metab. 2020; 105 (10): e3785–97. DOI: https://doi.org/10.1210/clinem/dgaa526 PMID: 32882036

42. Labadzhyan A., Nachtigall L.B., Freseriu M., Gordon M.B., Molitch M., Kennedy L., et al. Oral octreotide capsules for the treatment of acromegaly: comparison of 2 phase 3 trial results. Pituitary. 2021; 24 (6): 943–53. DOI: https://doi.org/10.1007/s11102-021-01163-2

43. Tiberg F., Roberts J., Cervin C., Johnsson M., Sarp S., Tripathi A.P., Linden M. Octreotide s.c. depot provides sustained octreotide bioavailability and similar IGF-1 suppression to octreotide LAR in healthy volunteers. Br J Clin Pharmacol. 2015; 80: 460–72. DOI: https://doi.org/10.1111/bcp.12698

44. Maffezzoni F., Formenti A.M., Mazziotti G., Frara S., Giustina A. Current and future medical treatments for patients with acromegaly. Expert Opin Pharmacother. 2016; 17 (12): 1631–42. DOI: https://doi.org/10.1080/14656566.2016.1199687

45. Madan A., Markison S., Betz S.F., Krasner A., Luo R., Jochelson T., et al. Paltusotine, a novel oral once-daily nonpeptide SST2 receptor agonist, suppresses GH and IGF-1 in healthy volunteers. Pituitary. 2022; 25 (2): 328–39. DOI: https://doi.org/10.1007/s11102-021-01201-z

46. Boon W.M.I., van Esdonk M.J., Stuurman F.E., Biermasz N.R., Pons L., Paty I., Burggraaf J. A novel somatostatin-dopamine chimera (BIM23B065) reduced GH secretion in a first-in-human clinical trial. J Clin Endocrinol Metab. 2019; 104 (3): 883–91. DOI: https://doi.org/10.1210/jc.2018-01364

47. Cuny T., Graillon T., Defilles C., Datta R., Zhang S., Figarella-Brander D., et al. Characterization of the ability of a, second-generation SST-DA chimeric molecule, TBR-065, to suppress GH secretion from human GH-secreting adenoma cells. Pituitary. 2021; 24 (3): 351–8. DOI: https://doi.org/10.1007/s11102-020-01113-4

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Ametov Alexander S.
Honored Scientist of the Russian Federation, Doctor of Medical Sciences, Professor, Head of Subdepartment of Endocrinology, Head of the UNESCO Network Chair on the subject «Bioethics of diabetes as a global problem» of the Russian Medical Academy of Continuous Professional Education (Moscow)
Вскрытие

Journals of «GEOTAR-Media»