, Volume 60, Issue 1, pp 15–27 | Cite as

The Zollinger-Ellison syndrome: is there a role for somatostatin analogues in the treatment of the gastrinoma?

  • Valentina Guarnotta
  • Chiara MartiniEmail author
  • Maria Vittoria Davì
  • Genoveffa Pizza
  • Annamaria Colao
  • Antongiulio Faggiano
  • on behalf of NIKE group



Analyze the role of somatostatin analogues (SSAs) in the treatment of sporadic and MEN1-related gastrinomas, trying to define whether recent trials have changed the landscape of gastrinoma therapy.


We evaluate the rationale of SSA use in the treatment of gastrinomas, summarize the current literature concerning the effect of SSAs on the control of Zollinger-Ellison syndrome (ZES) and gastrinomas tumor progression and discuss their role in the most recent guidelines.


The medical treatment of gastrinoma and related ZES is aimed at controlling acid hypersecretion and tumor progression, in inoperable patients. The use of proton pump inhibitors (PPIs) to control the syndrome is a cornerstone in the ZES therapy. SSAs are not usually indicated for antisecretory purpose, because PPIs are considered the treatment of choice, due to their long lasting high efficacy and oral availability. The antiproliferative effect of SSAs has been established by two placebo-controlled trials that have clearly demonstrated a significant increase in progression free survival in patients affected by non-functioning well-differentiated advanced neuroendocrine tumors (NETs). The recent ENETS guidelines recommend the use of SSAs in advanced well differentiated NETs as antiproliferative agents.


The high sstr-expression in gastrinomas make them highly responsive to SSAs and support the use of such drugs to counteract the tumour growth in patients not amenable to surgical cure. Unfortunately, limited data, mainly case reports or small series, support the use of SSAs in advanced gastrinomas, therefore, it is difficult to quantify their ability to control tumour growth and disease progression.


Somatostatin Somatostatin analogues Neuroendocrine tumours Gastrinoma 



This review is part of the ‘NIKE’ project (Neuroendocrine tumors Innovation Knowledge and Education) led by Prof Annamaria Colao, which aims at increasing the knowledge on NETs. We would like to acknowledge all the Collaborators of this project: Albertelli M., Amoroso V., Arvat E., Badalamenti G., Bajetta E., Baldelli R., Bianchi A., Botti G., Buzzoni R., Campana D., Carnaghi C., Cingarlini S., Circelli L., Corcione F., De Rosa G., degli Uberti E., Delle Fave G., Del Basso De Caro M.L., Di Sarno A., Falconi M., Fanciulli G., Ferolla P., Ferone D., Fiore F., Gallo M., Gaudenzi G., Giordano C., Giuffrida D., Grossrubatscher E., Guadagno E., Izzo F., Lania A., Lastoria S., Leo S., Lo Calzo F., Logoluso F., Malandrino P., Marchetti M., Marotta V., Mazzaferro V., Messina E., Milione M., Modica R., Montesarchio V., Muto P., Nappi O., Nazzari E., Panzuto F., Pia A., Piovesan A., Pontecorvi A., Pusceddu S., Razzore P., Riccardi F., Rindi G., Rota F., Scarpa A., Sciammarella C., Spada F., Tafuto S., Versari A., Vitale G., Volante M., Zatelli M.C.

Compliance with ethical standards

Conflict of interests

A.C and A.F report support to research from Novartis, Ipsen and Italfarmaco. The remaining authors declare that they have no competing interests.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Valentina Guarnotta
    • 1
  • Chiara Martini
    • 2
    Email author
  • Maria Vittoria Davì
    • 3
  • Genoveffa Pizza
    • 4
  • Annamaria Colao
    • 4
  • Antongiulio Faggiano
    • 5
  • on behalf of NIKE group
  1. 1.Biomedical Department of Internal and Specialist Medicine (DIBIMIS), Section of Endocrine-Metabolic DiseasesUniversity of PalermoPalermoItaly
  2. 2.Clinica Medica 3^, Department of Medicine, DIMEDUniversity of PadovaPadovaItaly
  3. 3.Section of Endocrinology, Medicina Generale e Malattie Aterotrombotiche e Degenerative, Department of MedicineUniversity of VeronaVeronaItaly
  4. 4.Department of Clinical Medicine and Surgery“Federico II” University of NaplesNaplesItaly
  5. 5.Thyroid and Parathyroid Surgery UnitIstituto Nazionale per lo studio e la cura dei tumori “Fondazione G. Pascale” – IRCCSNaplesItaly

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