This protocol applies to patients with advanced insulinoma — unresectable or metastatic disease — where a prior treatment line has failed to resolve hypoglycaemia, and a next-line intervention is required.

Clinical Scenario

Advanced insulinoma with unresectable or metastatic disease poses a complex management challenge. Because the tumour is functioning, controlling hypoglycaemia is a primary clinical goal alongside tumour-directed treatment. A multimodal approach — combining medical, interventional, and surgical strategies — is required in this setting.

Previous Line — Escalation Trigger

The preceding treatment — peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE or everolimus — did not achieve disappearance of hypoglycaemic symptoms. Failure to reach that goal is the clinical trigger for escalation to this protocol.

Next-Line Approach — Partial Overview

The protocol for this setting incorporates specific chemotherapy options and, for certain presentations, interventional approaches. The primary goal is control of hypoglycaemia. The complete regimen, agent selection criteria, and sequencing are available in the structured protocol below.

References

DOI: 10.1111/jne.13318

The management of functioning Pan-NET syndromes in patients with advanced disease, that is, unresectable or metastatic, requires a multimodal approach consisting of supportive, medical, interventional and surgical treatment.
Historically, streptozotocin is well-known for its diabetogenic effects, making it a suitable alternative for high grade or clinically aggressive insulinomas.
Radioembolisation together with chemoembolisation recently proved to be highly effective in controlling hypoglycaemia in a series of seven patients with malignant insulinoma, resulting in an initial clinical success rate of 100% and in an overall clinical success rate of 85%.

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Treatment of Advanced Insulinoma When PRRT with 177Lu-DOTATATE or Everolimus Has Not Eliminated Hypoglycaemic Symptoms