What are the medical treatment options for metastatic insulinoma?

Updated: May 31, 2020
  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Neetu Radhakrishnan, MD  more...
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Answer

The current medical treatment choices are those used for any metastatic neuroendocrine gastroenteric pancreatic tumor. Options are as follows:

  • Combination therapy with streptozotocin plus doxorubicin or 5-fluorouracil: Streptozotocin alone may achieve a partial response in 50% of patients and complete response in 20%. The median survival in one study was 16 months. With streptozotocin plus 5-fluorouracil, 33% of patients show complete response, with the median survival increasing to 26 months.
  • Dacarbazine- and temozolomide-based regimens: There appears to be a correlation between expression of methylguanine DNA methyltransferase (MGMT) and temozolomide responsiveness in advanced neuroendocrine tumors. MGMT is an enzyme that is responsible for DNA repair induced by alkylating agent chemotherapy.

  • Molecularly targeted therapy: This includes vascular endothelial growth factor receptor (VEGFR) inhibitors such as sunitinib, sorafenib, pazopanib, or cabozantinib.

  • Mammalian target of rapamycin (mTOr) inhibitors: Everolimus, with or without octreotide

  • Peptide receptor radioligand therapy: In January 2018, the US Food & Drug Administration approved lutetium [177Lu] oxodotreotide (Lutathera) for the treatment of patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors. Approval was based on results of the phase III NETTER-1 trial [44, 45]

The mTOR inhibitor everolimus is approved for treatment of locally advanced or metastatic neuroendocrine tumors of pancreatic origin. In a French study, everolimus therapy normalized blood glucose levels in 11 of 12 patients with metastatic insulinoma and refractory hypoglycemia, with the therapeutic effect maintained for a median duration of 6.5 months (range 1-35+ months). However, three patients discontinued everolimus because of cardiac and/or pulmonary adverse events, which led to two deaths. [46]  


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