Somatostatin analogue-induced pancreatic exocrine insufficiency in patients with neuroendocrine tumors: results of a prospective observational study

ABSTRACT

Background: Patients with advanced well-differentiated neuroendocrine tumours (Wd-NETs) are commonly treated with somatostatin analogues (SSAs). Some patients may develop SSA-related side effects such as pancreatic exocrine insufficiency (PEI).

Methods: In this prospective, observational study, the frequency of SSA-induced PEI in 50 sequential patients with advanced Wd-NETs treated with SSAs was investigated. Toxicity was assessed monthly and faecal elastase-1 (FE1) and quality of life (QoL) were assessed 3-monthly.

Results: The median age was 65.8 years, 58% were male and the majority (92%) of patients had metastatic disease; patients received 4-weekly long acting octreotide (60%) or lanreotide (40%). Twelve patients (24%) developed SSA-related PEI after a median of 2.9 months from SSA initiation; FE1 was a reliable screening tool for PEI, especially in symptomatic (abdominal bloating, flatulence and/or diarrhea) patients (risk ratio 8.25 (95% confidence interval 1.15–59.01)). Most of these patients (11/12; 92%) required PERT. Other SSA-related adverse events (any grade) included flatulence (50%), abdominal pain (32%), diarrhoea (30%) and fatigue (20%). Development of PEI did not significantly worsen overall QoL, however gastrointestinal symptoms and diarrhoea were increased.

Conclusion: This study demonstrated that PEI occurs at a higher rate than previously reported; clinicians need to diagnose and treat this SSA-related adverse-event which occurs in 1 in 4 patients with Wd-NETs treated with SSAs. Screening with FE1 in symtomatic patients is recommend.

KEYWORDS:

• Neuroendocrine tumours
• somatostatin analogues
• pancreatic exocrine insufficiency
• quality of life
• diarrhoea
• steatorrhoea

Declaration of interest

A Lamarca was partially-funded by the European Society for Medical Oncology (ESMO) Translational Fellowship Programme, the Spanish Society of Medical Oncology (SEOM) Fellowship Programme and by the ASCO Conquer Cancer Foundation Young Investigator Award. J Barriuso was partially-funded by the the Spanish Society of Medical Oncology (SEOM) Fellowship Programme and by the European Neuroendocrine Tumor Society (ENETS) CoE Excellence Academy Fellowship. This manuscript was developed with the support of STR (Systemic Therapies Research) (The Christie NHS Foundation Trust). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Dr Angela Lamarca was responsible for the study design, data collection, database creation, data analysis, interpretation of results and manuscript writing. Sister Lynne McCallum was responsible for the study design, data collection, database creation and interpretation of results. Dr Alison Backen was responsible for data analysis, interpretation of results and manuscript writing. Sister Christina Nuttall, Dr Jorge Barriuso, Dr Melissa Frizziero, Dr Rebecca Leon, Dr Wasat Mansoor, Dr Mairéad G McNamara and Dr Richard Hubner were all responsible for data collection and interpretation of results. Professor Juan W Valle was responsible for the study design, data collection and interpretation of results. All authors were involved in the manuscript preparation and approval of the final version.

Supplementary material

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Additional information

Funding

The manuscript was not funded.