SpringerLink
Log in

Efficacy and tolerability of somatostatin analogues according to gender in patients with neuroendocrine tumors

  • Published:
Reviews in Endocrine and Metabolic Disorders Aims and scope Submit manuscript

Abstract

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

AR:

Androgen Receptor

BMI:

Body mass index

CaS:

Carcinoid Syndrome

ERα:

Estrogen receptor alpha

ERβ:

Estrogen receptor beta

E2:

Estradiol

GEP-NET:

Gastroenteropancreatic Neuroendocrine Tumors

GH:

Growth hormone

H3K4:

Histone H3 lysine K4

MEN1:

Multiple endocrine neoplasia type 1

MENX:

Multiple Endocrine Neoplasia X

NEC:

Neuroendocrine Carcinomas

NEN:

Neuroendocrine Neoplasms

NET:

Neuroendocrine Tumors

NF pit-NET:

Non-functioning pituitary tumors

PET:

Positron emission tomography

pitNET:

Pituitary tumors

PR:

Progesteron receptor

PRRT:

Peptide-receptor radionuclide therapy

SI-NET:

Small-intestine Neuroendocrine Tumors

SSA:

Somatostatin Analogues

SST:

Somatostatin

SSTR:

Somatostatin receptors

SUV:

Standardized uptake value

TFF1:

Trefoil factor 1

VDR:

Vitamin D receptor

References

  1. de Herder WW. When and how to use somatostatin analogues. Endocrinol Metab Clin North Am. 2018;47:549–55. https://doi.org/10.1016/j.ecl.2018.04.010.

    Article  PubMed  Google Scholar 

  2. Faggiano A. Long-acting somatostatin analogs and well differentiated neuroendocrine tumors: a 20-year-old story. J Endocrinol Invest. 2023. https://doi.org/10.1007/s40618-023-02170-9.10.1007/s40618-023-02170-9.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004;15:966–73. https://doi.org/10.1093/annonc/mdh216.

    Article  CAS  PubMed  Google Scholar 

  4. Ferolla P, Faggiano A, Mansueto G, Avenia N, Cantelmi MG, Giovenali P, et al. The biological characterization of neuroendocrine tumors: The role of neuroendocrine markers. J Endocrinol Invest. 2008;31:277–86. https://doi.org/10.1007/BF03345602.

    Article  CAS  PubMed  Google Scholar 

  5. Faggiano A, Ferolla P, Grimaldi F, Campana D, Manzoni M, Davì MV, et al. Natural history of gastro-entero-pancreatic and thoracic neuroendocrine tumors. Data from a large prospective and retrospective Italian Epidemiological study: The net management study. J Endocrinol Invest. 2012;35:817–23. https://doi.org/10.3275/8102.

    Article  CAS  PubMed  Google Scholar 

  6. Asa SL, Mete O, Perry A, Osamura RY. Overview of the 2022 WHO classification of pituitary tumors. Endocr Pathol. 2022;33:6–26. https://doi.org/10.1007/s12022-022-09703-7.

    Article  CAS  PubMed  Google Scholar 

  7. Piscopo L, Zampella E, Pellegrino S, Volpe F, Nappi C, Gaudieri V, Fonti R, Vecchio SD, Cuocolo A, Klain M. Diagnosis, management and theragnostic approach of gastro-entero-pancreatic neuroendocrine neoplasms. Cancers. 2023;15:3483. https://doi.org/10.3390/cancers15133483.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017;376(2):125–35. https://doi.org/10.1056/NEJMoa1607427.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Niederle MB, Hackl M, Kaserer K, Niederle B. Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. Endocr Relat Cancer. 2010;17(4):909–18.

    Article  PubMed  Google Scholar 

  10. Halperin DM, Shen C, Dasari A, Xu Y, Chu Y, Zhou S, et al. Frequency of carcinoid syndrome at neuroendocrine tumour diagnosis: a population-based study. Lancet Oncol. 2017;18:525–34.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Muscogiuri G, Altieri B, Albertelli M, et al. Epidemiology of pancreatic neuroendocrine neoplasms: a gender perspective. Endocrine. 2020;69(2):441–50. https://doi.org/10.1007/s12020-020-02331-3.

    Article  CAS  PubMed  Google Scholar 

  12. Ruggeri RM, Altieri B, Grossrubatcher E, Minotta R, Tarsitano MG, Zamponi V, Isidori AM, Faggiano A, Colao AM, NIKE Group. Sex differences in carcinoid syndrome: A gap to be closed. Rev Endocr Metab Disord. 2022;23:659–69. https://doi.org/10.1007/s11154-022-09719-8.

    Article  PubMed  Google Scholar 

  13. White BE, Russell B, Remmers S, Rous B, Chandrakumaran K, Wong KF, Van Hemelrijck M, Srirajaskanthan R, Ramage JK. Sex differences in survival from neuroendocrine neoplasia in England 2012–2018: A retrospective, population-based study. Cancers (Basel). 2023;15:1863. https://doi.org/10.3390/cancers15061863.

    Article  PubMed  Google Scholar 

  14. Patel YC. Somatostatin and its receptor family. Front Neuroendocrinol. 1999;20:157–98.

    Article  CAS  PubMed  Google Scholar 

  15. Eigler T, Ben-Shlomo A. Somatostatin system: Molecular mechanisms regulating anterior pituitary hormones. J Mol Endocrinol. 2014;53:R1–19.

    Article  CAS  PubMed  Google Scholar 

  16. Rorsman P, Huising MO. The somatostatin-secreting pancreatic delta-cell in health and disease. Nat Rev Endocrinol. 2018;14:404–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pyronnet S, Bousquet C, Najib S, Azar R, Laklai H, Susini C. Antitumor effects of somatostatin. Mol Cell Endocrinol. 2008;286:230–7.

    Article  CAS  PubMed  Google Scholar 

  18. Møller LN, Stidsen CE, Hartmann B, Holst JJ. Somatostatin receptors. Biochim Biophys Acta. 2003;1616:1–84. https://doi.org/10.1016/s0005-2736(03)00235-9.

    Article  PubMed  Google Scholar 

  19. Modlin IM, Pavel M, Kidd M, Gustafsson BI. Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther. 2010;31:169–88. https://doi.org/10.1111/j.1365-2036.2009.04174.x.

    Article  CAS  PubMed  Google Scholar 

  20. Cives M, Strosberg J. The expanding role of somatostatin analogs in gastroenteropancreatic and lung neuroendocrine tumors. Drugs. 2015;75:847–58. https://doi.org/10.1007/s40265-015-0397-7.

    Article  CAS  PubMed  Google Scholar 

  21. Pöll F, Lehmann D, Illing S, Ginj M, Jacobs S, Lupp A, Stumm R, Schulz S. Pasireotide and octreotide stimulate distinct patterns of sst2A somatostatin receptor phosphorylation. Mol Endocrinol. 2010;24:436–46. https://doi.org/10.1210/me.2009-0315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gatto F, Barbieri F, Arvigo M, Thellung S, Amarù J, Albertelli M, Ferone D, Florio T. Biological and biochemical basis of the differential efficacy of first and second generation somatostatin receptor ligands in neuroendocrine neoplasms. Int J Mol Sci. 2019;20:3940. https://doi.org/10.3390/ijms20163940.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gatto F, Arvigo M, Ferone D. Somatostatin receptor expression and patients’ response to targeted medical treatment in pituitary tumors: evidences and controversies. J Endocrinol Invest. 2020;43:1543–53. https://doi.org/10.1007/s40618-020-01335-0.

    Article  CAS  PubMed  Google Scholar 

  24. Hofland LJ, van der Hoek J, Feelders R, van Aken MO, van Koetsveld PM, Waaijers M, Sprij-Mooij D, Bruns C, Weckbecker G, de Herder WW, Beckers A, Lamberts SW. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol. 2005;152:645–54. https://doi.org/10.1530/eje.1.01876.

    Article  CAS  PubMed  Google Scholar 

  25. Gatto F, Feelders RA, Franck SE, van Koetsveld PM, Dogan F, Kros JM, Neggers SJCMM, van der Lely AJ, Lamberts SWJ, Ferone D, Hofland LJ. In vitro head-to-head comparison between octreotide and pasireotide in GH-secreting pituitary adenomas. J Clin Endocrinol Metab. 2017;102:2009–18. https://doi.org/10.1210/jc.2017-00135.

    Article  PubMed  Google Scholar 

  26. Hofland LJ, van der Hoek J, van Koetsveld PM, de Herder WW, Waaijers M, Sprij-Mooij D, Bruns C, Weckbecker G, Feelders R, van der Lely AJ, Beckers A, Lamberts SW. The novel somatostatin analog SOM230 is a potent inhibitor of hormone release by growth hormone- and prolactin-secreting pituitary adenomas in vitro. J Clin Endocrinol Metab. 2004;89:1577–85. https://doi.org/10.1210/jc.2003-031344.P.

    Article  CAS  PubMed  Google Scholar 

  27. Vázquez-Borrego MC, Gupta V, Ibáñez-Costa A, Gahete MD, Venegas-Moreno E, Toledano-Delgado Á, et al. A somatostatin receptor subtype-3 (SST3) peptide agonist shows antitumor effects in experimental models of nonfunctioning pituitary tumors. Clin Cancer Res. 2020;26:957–69. https://doi.org/10.1158/1078-0432.CCR-19-2154.

    Article  PubMed  Google Scholar 

  28. Chan DL, Ferone D, Albertelli M, Pavlakis N, Segelov E, Singh S. Escalated-dose somatostatin analogues for antiproliferative effect in GEPNETS: A systematic review. Endocrine. 2017;57:366–75.

    Article  CAS  PubMed  Google Scholar 

  29. Mohamed A, Blanchard MP, Albertelli M, Barbieri F, Brue T, Niccoli P, et al. Pasireotide and octreotide antiproliferative effects and sst2 trafficking in human pancreatic neuroendocrine tumor cultures. Endocr Relat Cancer. 2014;21:691–704. https://doi.org/10.1530/ERC-14-0086.

    Article  CAS  PubMed  Google Scholar 

  30. Vitale G, Dicitore A, Sciammarella C, Di Molfetta S, Rubino M, Faggiano A, Colao A. Pasireotide in the treatment of neuroendocrine tumors: A review of the literature. Endocr Relat Cancer. 2018;25:R351–64.

    Article  CAS  PubMed  Google Scholar 

  31. Mogl MT, Dobrindt EM, Buschermöhle J, Bures C, Pratschke J, Amthauer H, Wetz C, Jann H. Influence of gender on therapy and outcome of neuroendocrine tumors of gastroenteropancreatic origin: A single-center analysis. Visc Med. 2020;36:20–7. https://doi.org/10.1159/000505500.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Abdel-Rahman O, Fazio N. Sex-based differences in prognosis of patients with gastroenteropancreatic-neuroendocrine neoplasms: A population-based study. Pancreas. 2021;50:727–31.

    Article  CAS  PubMed  Google Scholar 

  33. Dufourny L, Warembourg M. Colocalization of progesterone receptor and somatostatin immunoreactivities in the hypothalamus of the male and female guinea pig. Neuroendocrinology. 1996;64:215–24.

    Article  CAS  PubMed  Google Scholar 

  34. Babu A, Luque RM, Glick R, Utset M, Fogelfeld L. Variability in quantitative expression of receptors in nonfunctioning pituitary macroadenomas–an opportunity for targeted medical therapy. Endocr Pract. 2014;20:15–25.

    Article  PubMed  Google Scholar 

  35. Bouyer K, Loudes C, Robinson IC, Epelbaum J, Faivre-Bauman A. Sexually dimorphic distribution of sst2A somatostatin receptors on growth hormone-releasing hormone neurons in mice. Endocrinology. 2006;147:2670–4.

    Article  CAS  PubMed  Google Scholar 

  36. Canosa LF, Lin X, Peter RE. Effects of sex steroid hormones on the expression of somatostatin receptors sst1 and sst5 in goldfish pituitary and forebrain. Neuroendocrinology. 2003;78:81–9.

    Article  CAS  PubMed  Google Scholar 

  37. Bouyer K, Faivre-Bauman A, Robinson IC, Epelbaum J, Loudes C. Sexually dimorphic distribution of sst2A receptors on growth hormone-releasing hormone neurones in mice: modulation by gonadal steroids. J Neuroendocrinol. 2008;20:1278–87.

    Article  CAS  PubMed  Google Scholar 

  38. Gulde S, Wiedemann T, Schillmaier M, Valença I, Lupp A, Steiger K, et al. Gender-specific efficacy revealed by head-to-head comparison of pasireotide and octreotide in a representative in vivo model of nonfunctioning pituitary tumors. Cancers (Basel). 2021;13:3097. https://doi.org/10.3390/cancers13123097.

    Article  CAS  PubMed  Google Scholar 

  39. Paragliola RM, Corsello SM, Salvatori R. Somatostatin receptor ligands in acromegaly: clinical response and factors predicting resistance. Pituitary. 2017;20:109–15.

    Article  CAS  PubMed  Google Scholar 

  40. Fleseriu M, Biller BMK, Freda PU, Gadelha MR, Giustina A, Katznelson L, Molitch ME, Samson SL, Strasburger CJ, van der Lely AJ, Melmed S. A Pituitary Society update to acromegaly management guidelines. Pituitary. 2021;24:1–13.

    Article  PubMed  Google Scholar 

  41. Ruggeri RM, Benevento E, De Cicco F, Grossrubatcher E, Hasballa I, Tarsitano MG, Centello R, Isidori AM, Faggiano A, Colao AM, NIKE Group. Multiple endocrine neoplasia type 4 (MEN4): a thorough update on the latest and least known men syndrome. Neuroendocrine neoplasms in the context of inherited tumor syndromes: a reappraisal focused on targeted therapies. J Endocrinol Invest. 2023;46:213–34. https://doi.org/10.1007/s40618-022-01905-4.

    Article  CAS  PubMed  Google Scholar 

  42. Imachi H, Murao K, Dobashi H, Bhuyan MM, Cao X, Kontani K, Niki S, Murazawa C, Nakajima H, Kohno N, Yamashita H, Iwase H, Hayashi S, Ishida T, Yamauchi A. Menin, a product of the MENI gene, binds to estrogen receptor to enhance its activity in breast cancer cells: possibility of a novel predictive factor for tamoxifen resistance. Breast Cancer Res Treat. 2010;122:395–407. https://doi.org/10.1007/s10549-009-0581-0.

    Article  CAS  PubMed  Google Scholar 

  43. Dreijerink KM, Mulder KW, Winkler GS, Höppener JW, Lips CJ, Timmers HT. Menin links estrogen receptor activation to histone H3K4 trimethylation. Cancer Res. 2006;66:4929–35. https://doi.org/10.1158/0008-5472.CAN-05-4461.

    Article  CAS  PubMed  Google Scholar 

  44. Alabraba EB, Taniere P, Reynolds GM, Stewart PM, Wigmore SJ, Bramhall SR. Expression and functional consequences of oestrogen and progesterone receptors in human insulinomas. Endocr Relat Cancer. 2007;14:1081–8. https://doi.org/10.1677/ERC-07-0093.

    Article  CAS  PubMed  Google Scholar 

  45. Qiu W, Christakis I, Stewart AA, Vodopivec DM, Silva-Figueroa A, Chen H, Woodard TL, Halperin DM, Lee JE, Yao JC, Perrier ND. Is estrogen exposure a protective factor for pancreatic neuroendocrine tumours in female patients with multiple endocrine neoplasia syndrome type 1? Clin Endocrinol (Oxf). 2017;86:791–7. https://doi.org/10.1111/cen.13324.

    Article  CAS  PubMed  Google Scholar 

  46. Estrella JS, Ma LT, Milton DR, Yao JC, Wang H, Rashid A, Broaddus RR. Expression of estrogen-induced genes and estrogen receptor β in pancreatic neuroendocrine tumors: implications for targeted therapy. Pancreas. 2014;43:996–1002. https://doi.org/10.1097/MPA.0000000000000203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Zimmermann N, Lazar-Karsten P, Keck T, Billmann F, Schmid S, Brabant G, Thorns C. Expression pattern of CDX2, estrogen and progesterone receptors in primary gastroenteropancreatic neuroendocrine tumors and metastases. Anticancer Res. 2016;36:921–4.

    CAS  PubMed  Google Scholar 

  48. Viale G, Doglioni C, Gambacorta M, Zamboni G, Coggi G, Bordi C. Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin. Cancer. 1992;70:2268–77.

    Article  CAS  PubMed  Google Scholar 

  49. Arnason T, Sapp HL, Barnes PJ, Drewniak M, Abdolell M, Rayson D. Immunohistochemical expression and prognostic value of ER, PR and HER2/neu in pancreatic and small intestinal neuroendocrine tumors. Neuroendocrinology. 2011;93:249–58.

    Article  CAS  PubMed  Google Scholar 

  50. Konukiewitz B, Schlitter AM, Jesinghaus M, Pfister D, Steiger K, Segler A, Agaimy A, Sipos B, Zamboni G, Weichert W, Esposito I, Pfarr N, Klöppel G. Somatostatin receptor expression related to TP53 and RB1 alterations in pancreatic and extrapancreatic neuroendocrine neoplasms with a Ki67-index above 20. Mod Pathol. 2017;30:587–98.

    Article  CAS  PubMed  Google Scholar 

  51. Blažević A, Iyer AM, van Velthuysen MF, Hofland J, Oudijk L, de Herder WW, Hofland LJ, Feelders RA. Sexual dimorphism in small-intestinal neuroendocrine tumors: Lower prevalence of mesenteric disease in premenopausal women. J Clin Endocrinol Metab. 2022;107:e1969–75.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Hallet J, Law CH, Cukier M, Saskin R, Liu N, Singh S. Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes. Cancer. 2015;121:589–97.

    Article  PubMed  Google Scholar 

  53. Oberg K, Norheim I, Theodorsson E. Treatment of malignant midgut carcinoid tumours with a long-acting somatostatin analogue octreotide. Acta Oncol. 1991;30:503–7.

    Article  CAS  PubMed  Google Scholar 

  54. Panzuto F, Di Fonzo M, Iannicelli E, Sciuto R, Maini CL, Capurso G, Milione M, Cattaruzza MS, Falconi M, David V, Ziparo V, Pederzoli P, Bordi C, Delle FG. Long-term clinical outcome of somatostatin analogues for treatment of progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinoma. Ann Oncol. 2006;17:461–6. https://doi.org/10.1093/annonc/mdj113.

    Article  CAS  PubMed  Google Scholar 

  55. Anthony L, Vinik AI. Evaluating the characteristics and the management of patients with neuroendocrine tumors receiving octreotide LAR during a 6-year period. Pancreas. 2011;40:987–94. https://doi.org/10.1097/MPA.0b013e31821f66b4.

    Article  CAS  PubMed  Google Scholar 

  56. Lamberti G, Faggiano A, Brighi N, Tafuto S, Ibrahim T, Brizzi MP, et al. Nonconventional doses of somatostatin analogs in patients with progressing well-differentiated neuroendocrine tumor. J Clin Endocrinol Metab. 2020;105:dgz035. https://doi.org/10.1210/clinem/dgz035.

    Article  PubMed  Google Scholar 

  57. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA. Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrome treatment (elect): a randomized, double-blind, placebo-controlled trial. Endocr Pract. 2016;22:1068–80.

    Article  PubMed  Google Scholar 

  58. Fisher GA Jr, Wolin EM, Liyanage N, Lowenthal SP, Mirakhur B, Pommier RF, et al. Lanreotide therapy in carcinoid syndrome: prospective analysis of patient-reported symptoms in patients responsive to prior octreotide therapy and patients naïve to somatostatin analogue therapy in the elect phase 3 study. Endocr Pract. 2018;24:243–55.

    Article  PubMed  Google Scholar 

  59. Lee SY, Choi YJ, Chang WJ, Shin SW, Kim YH, Kim ST. The role of chemotherapy and/or octreotide in patients with metastatic gastroenteropancreatic and hepatobiliary neuroendocrine carcinoma. J Gastrointest Oncol. 2014;5:457–62. https://doi.org/10.3978/j.issn.2078-6891.2014.075.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Palazzo M, Lombard-Bohas C, Cadiot G, et al. Ki67 proliferation index, hepatic tumor load, and pretreatment tumor growth predict the antitumoral efficacy of lanreotide in patients with malignant digestive neuroendocrine tumors. Eur J Gastroenterol Hepatol. 2013;25:232–8. https://doi.org/10.1097/MEG.0b013e328359d1a6.

    Article  CAS  PubMed  Google Scholar 

  61. Ruggeri RM, Altieri B, Razzore P, Retta F, Sperti E, Scotto G, NIKE Group, et al. JEI J Endocrinol Invest. 2023. https://doi.org/10.1007/s40618-023-02213-1.

    Article  Google Scholar 

  62. Laskaratos FM, Walker M, Naik K, et al. Predictive factors of antiproliferative activity of octreotide LAR as first-line therapy for advanced neuroendocrine tumours. Br J Cancer. 2016;115:1321–7. https://doi.org/10.1038/bjc.2016.349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Shen C, Xu Y, Dasari A, Shih YC, Yao JC. Octreotide LAR dosage and survival among elderly patients with distant-stage neuroendocrine tumors. Oncologist. 2016;21:308–13. https://doi.org/10.1634/theoncologist.2015-0381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. 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. https://doi.org/10.2165/0003088-200948010-00004.

    Article  PubMed  Google Scholar 

  65. Joseph S, Li G, Lindholm E, et al. A prospective trial on the effect of body mass index and sex on plasma octreotide levels in patients undergoing long-term octreotide LAR therapy. Pancreas. 2010;39:964–6. https://doi.org/10.1097/MPA.0b013e3181db01a8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Delle Fave G, O’Toole D, Sundin A. ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms. Neuroendocrinology. 2016;103:119–24. https://doi.org/10.1159/000443168.

    Article  CAS  PubMed  Google Scholar 

  67. Leisser A, Lukic K, Nejabat M. Sex-differences in [68Ga] Ga-DOTANOC biodistribution. Nucl Med Biol. 2019;76–77:15–20. https://doi.org/10.1016/j.nucmedbio.2019.08.005.

    Article  CAS  PubMed  Google Scholar 

  68. Sandstrom M, Ilan E, Sundin A, Lubberink M. Is there a gender difference of absorbed dose to the risk organs in patients receiving 177Lu-Octreotate therapy? J Nuclear Med. 2017;58(supplement 1):248.

    Google Scholar 

  69. Nilica B, Svirydenka A, Fritz J, Bayerschmidt S, Kroiss AS, Gruber L, Virgolini IJ. Nephrotoxicity and hematotoxicity one year after four cycles of peptide receptor radionuclide therapy (PRRT) and its impact on future treatment planning. A retrospective analysis. Rev Esp Med Nucl Imagen Mol (Engl Ed). 2021;S2253–654X(21)00062–7. https://doi.org/10.1016/j.remn.2021.03.004.

  70. Saracyn M, Durma AD, Bober B, Kołodziej M, Lubas A, Kapusta W, Niemczyk S, Kamiński G. Long-term complications of radioligand therapy with lutetium-177 and yttrium-90 in patients with neuroendocrine neoplasms. Nutrients. 2022;15:185. https://doi.org/10.3390/nu15010185.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bodei L, Kidd M, Paganelli G, Grana CM, Drozdov I, Cremonesi M, Lepensky C, Kwekkeboom DJ, Baum RP, Krenning EP, Modlin IM. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors. Eur J Nucl Med Mol Imaging. 2015;42:5–19. https://doi.org/10.1007/s00259-014-2893-5.

    Article  CAS  PubMed  Google Scholar 

  72. Sabolic I, Asif AR, Budach WE, Wanke C, Bahn A, Burckhardt G. Gender differences in kidney function. Pflugers Arch. 2007;455:397–429. https://doi.org/10.1007/s00424-007-0308-1.

    Article  CAS  PubMed  Google Scholar 

  73. Bergsma H, Konijnenberg MW, Kam BL, Teunissen JJ, Kooij PP, de Herder WW, Franssen GJ, van Eijck CH, Krenning EP. Kwekkeboom DJ Subacute haematotoxicity after PRRT with (177) Lu-DOTA-octreotate: prognostic factors, incidence and course. Eur J Nucl Med Mol Imaging. 2016;43:453–63. https://doi.org/10.1007/s00259-015-3193-4.

    Article  CAS  PubMed  Google Scholar 

  74. Minczeles NS, de Herder WW, Konijnenberg MW, Feelders RA, Brabander T, Hofland J. Dose-limiting bone marrow toxicities after peptide receptor radionuclide therapy are more prevalent in women than in men. Clin Nucl Med. 2022;47:599–605. https://doi.org/10.1097/RLU.0000000000004203.

    Article  PubMed  Google Scholar 

  75. Señarís RM, Lago F, Diéguez C. Gonadal regulation of somatostatin receptor 1, 2 and 3 mRNA levels in the rat anterior pituitary. Brain Res Mol Brain Res. 1996;38:171–5.

    Article  PubMed  Google Scholar 

  76. Campana D, Capurso G, Partelli S, Nori F, Panzuto F, Tamburrino D, Cacciari G, Delle Fave G, Falconi M, Tomassetti P. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence. Eur J Nucl Med Mol Imaging. 2013;40:1197–205. https://doi.org/10.1007/s00259-013-2402-2.

    Article  CAS  PubMed  Google Scholar 

  77. Carlsen EA, Fazio N, Granberg D, Grozinsky-Glasberg S, Ahmadzadehfar H, Grana CM, Zandee WT, Cwikla J, Walter MA, Oturai PS, Rinke A, Weaver A, Frilling A, Gritti S, Arveschoug AK, Meirovitz A, Knigge U, Sorbye H. Peptide receptor radionuclide therapy in gastroenteropancreatic NEN G3: a multicenter cohort study. Endocr Relat Cancer. 2019;26:227–39. https://doi.org/10.1530/ERC-18-0424.

    Article  CAS  PubMed  Google Scholar 

  78. Abou Jokh Casas E, Pubul Núñez V, Anido-Herranz U, Del Carmen Mallón Araujo M, Del Carmen Pombo Pasín M, Garrido Pumar M, Cabezas Agrícola JM, Cameselle-Teijeiro JM, Hilal A, Ruibal Morell Á. Evaluation of 177Lu-Dotatate treatment in patients with metastatic neuroendocrine tumors and prognostic factors. World J Gastroenterol. 2020;26:1513–24. https://doi.org/10.3748/wjg.v26.i13.1513.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Paganelli G, Sansovini M, Nicolini S, Grassi I, Ibrahim T, Amadori E, Di Iorio V, Monti M, Scarpi E, Bongiovanni A, Altini M, Urso L, Cittanti C, Matteucci F, Severi S. 177Lu-PRRT in advanced gastrointestinal neuroendocrine tumors: 10-year follow-up of the IRST phase II prospective study. Eur J Nucl Med Mol Imaging. 2021;48:152–60. https://doi.org/10.1007/s00259-020-04873-0.

    Article  PubMed  Google Scholar 

  80. Kipnis ST, Hung M, Kumar S, Heckert JM, Lee H, Bennett B, Soulen MC, Pryma DA, Mankoff DA, Metz DC, Eads JR, Katona BW. Laboratory, clinical, and survival outcomes associated with peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. JAMA. 2021;4:e212274. https://doi.org/10.1001/jamanetworkopen.2021.2274.

    Article  Google Scholar 

  81. Satapathy S, Mittal BR, Sood A, Sood A, Kapoor R, Gupta R, Khosla D. 177Lu-DOTATATE plus radiosensitizing capecitabine versus octreotide long-acting release as first-line systemic therapy in advanced grade 1 or 2 gastroenteropancreatic neuroendocrine tumors: a single-institution experience. JCO Glob Oncol. 2021;7:1167–75. https://doi.org/10.1200/GO.21.00103.

    Article  PubMed  Google Scholar 

  82. Vaughan E, Machta J, Walker M, Toumpanakis C, Caplin M, Navalkissoor S. Retreatment with peptide receptor radionuclide therapy in patients with progressing neuroendocrine tumours: efficacy and prognostic factors for response. Br J Radiol. 2018;91:20180041. https://doi.org/10.1259/bjr.20180041.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Zacho MD, Iversen P, Villadsen GE, Baunwall SMD, Arveschoug AK, Grønbaek H, Dam G. Clinical efficacy of first and second series of peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm: a cohort study. Scand J Gastroenterol. 2021;56(3):289–97. https://doi.org/10.1080/00365521.2021.1872095.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study is part of the ‘Neuroendocrine Tumors Innovation Knowledge and Education’ project led by Prof. Antongiulio Faggiano, Prof. Andrea M. Isidori, and Prof. Annamaria Colao, which aims at increasing the knowledge on neuroendocrine tumors. We would like to acknowledge all the Collaborators of the “NIKE” project: M. Albertelli, I. Alessi, B. Altieri, S. Antonini, L. Barrea, E. Benevento F. Birtolo, F. Campolo, G. Cannavale, C. Cantone, S. Carra, R. Centello, A. Cozzolino, F. De Cicco, S. Di Molfetta, V. Di Vito, G. Fanciulli, T. Feola, F. Ferraù, E. Giannetta, F. Grillo, E. Guadagno, V. Guarnotta, I. Hasballa A. La Salvia, A. Laffi, A. Lania, A. Liccardi, P. Malandrino, R. Mazzilli, E. Messina, N. Mikovic, R. Minotta, R. Modica, C. Pandozzi, G. Pugliese, G. Puliani, A. Ragni, M. Rubino, F. Russo, F. Sesti, L. Verde, A. Veresani, C. Vetrani, G. Vitale, I. Zanata.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV, University of Messina, 98125, Messina, Italy

    Rosaria M. Ruggeri

  2. Endocrinology Unit, Azienda Ospedaliera Universitaria Sassari, Sassari, Italy

    Irene Aini

  3. Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

    Stefano Gay

  4. Endocrine Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy

    Erika Maria Grossrubatscher

  5. Unit of Andrology and Endocrinology, Department of Clinical and Molecular Medicine, Sapienza University of Rome, 00189, Rome, Italy

    Camilla Mancini

  6. Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy

    Maria Grazia Tarsitano

  7. Endocrinology Unit, Department of Clinical and Molecular Medicine, SantʼAndrea Hospital, ENETS Center of Excellence, Sapienza University of Rome, Rome, Italy

    Virginia Zamponi & Antongiulio Faggiano

  8. Policlinico Umberto I, Università Sapienza, Gruppo NETTARE, Rome, Italy

    Andrea M. Isidori

  9. Endocrinology, Diabetology and Andrology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy

    Annamaria Colao

  10. UNESCO Chair “Education for Health and Sustainable Development”, Federico II University, Naples, Italy

    Annamaria Colao

Authors
  1. Rosaria M. Ruggeri
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Irene Aini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefano Gay
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erika Maria Grossrubatscher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Camilla Mancini
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maria Grazia Tarsitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Virginia Zamponi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea M. Isidori
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Annamaria Colao
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Antongiulio Faggiano
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

NIKE group

Contributions

Each Author gave a substantial contribute to the paper and approved the final version to be published. R.M.R., I.A., S.G., E.G., C.M., M.G.T., and V.Z. made substantial contributions to the conception of the article, literature search and wrote the manuscript. A.I., A.F., and A.C. critically revised the work for important intellectual content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rosaria M. Ruggeri.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Competing interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruggeri, R.M., Aini, I., Gay, S. et al. Efficacy and tolerability of somatostatin analogues according to gender in patients with neuroendocrine tumors. Rev Endocr Metab Disord 25, 383–398 (2024). https://doi.org/10.1007/s11154-023-09858-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11154-023-09858-6

Keywords

Search

Navigation