Treatment of Carcinoid Syndrome in Small Intestine NET When Somatostatin Analogues Have Failed

Clinical scenario

This protocol applies to patients with small intestine neuroendocrine tumour (Si-NET) presenting with carcinoid syndrome — characterised by diarrhoea and flushing arising from secretion of biologically active compounds. Patients with carcinoid syndrome are managed on a distinct treatment pathway from those with non-functioning Si-NET.

Previous line — goals not achieved

First-line therapy with somatostatin analogues (octreotide LAR or lanreotide autogel), including short-acting octreotide for breakthrough symptoms, did not achieve adequate symptomatic control of diarrhoea and flushing or sufficient reduction of 5-HIAA levels. This constitutes refractory carcinoid syndrome and is the indication for the next treatment step.

Next-line approach (partial overview)

For refractory carcinoid syndrome with persistent diarrhoea, the approach includes adding an oral agent targeting serotonin synthesis to ongoing SSA therapy — with further escalation strategies detailed in the full protocol.

Treatment goals

Reduction of diarrhoea and reduction of 5-HIAA levels.

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References

DOI: 10.1111/jne.13423

It is important to note that patients suffering from CS are treated differently from patients with non-functioning Si-NET.

Some patients present with specific symptoms of the carcinoid syndrome (CS) due to secretion of biologically active compounds such as serotonin and tachykinins or are discovered during surgery for intestinal obstruction or bleeding.

In patients with refractory CS and predominant diarrhoea, telotristat ethyl should be added to SSA (Recommendation A-1a).

SSA dose escalation can be considered in patients with refractory CS (Recommendation A-3b) or alternatively addition of IFN-α (Recommendation B-2b).

Telotristat ethyl, an oral inhibitor of the serotonin synthesis, significantly reduced diarrhoea and 5-HIAA levels in patients with refractory CS in two randomised placebo-controlled trials.

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