Insulinoma medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

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Overview

Medical therapy is reserved for those who can't undergo the primary surgical therapy. Drugs commonly used for benign insulinoma are Diazoxide, Octreotide/lanreotide, Phenytoin, verapamil and everolimus. For malignant insulinoma, these drugs are used with the chemotherapy drugs Streptozocin, 5 Fluorouracil, Doxorubicin, bevacizumab and Capecitabine in different combinations. For metastasis mainly going to liver regimens include hepatic artery embolization, radiation, chemo-embolization, ethanol ablation Radiofrequency ablation and Cryoablation.

Medical Therapy

• The primary treatment is surgical excision. Medical therapy is reserved for:
  • Those who can't undergo surgery
    • High-risk patients
    • Unresectable metastatic disease
  • Those who refuse to undergo surgery
• The medical therapy is mainly used to reduce/prevent symptoms of hypoglycemia.
• Pharmacologic medical therapies for insulinoma include diazoxide, octreotide/lanreotide, phenytoin, verapamil, and everolimus.

1. Adult

• Parenteral
  • Preferred regimen (1): Octreotide 30 mg IM (depot) every 4 weeks until tumor progression or death.
  • Preferred regimen (2): Octreotide 100-500 μg SQ q 8-12h（can be increased to maximum 1500 μg daily）for 1 year.
  • Preferred regimen (3): Lanreotide 120 mg SQ every 4 weeks until tumor progression.
• Oral
  • Preferred regimen : Diazoxide 3-8 mg/kg OR 200-300 mg PO q8h for 14-21 days (1200 mg max to be divided in 3 doses and max is 400 mg/dose).
  • Alternative regimen (1): Phenytoin 300-600 mg PO q daily.
  • Alternative regimen (2): Everolimus 10 mg PO q daily until disease progression.
  • Verapamil and Propranolol to control symptoms are used either as alone or in combination.
  • Glucocorticoids and Glucagon have been used in combination with diazoxide.

2. Pediatric

2.1 Neonates and Infants:

• Oral
  • Preferred regimen: Diazoxide initial dose: 10 mg/kg/day divided into 3 equal doses q 8 hours.
  • Maintenance dosing range: 8 to 15 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours.
    

2.2 Children and adolescents- follow the adult regimen

Malignant (metastatic) Insulinoma

Chemotherapy
It is used in the different combination of the following drugs:

• Streptozocin 500 mg/m²/day IV for 5 consecutive days every 6 weeks
• Doxorubicin 40-75 mg/m² IV every 21 to 28 days
• 5 Fluorouracil(5-FU)
• Temozolamide 200 mg/m² PO QHS days 10 to 14 of a 28-day treatment cycle (in combination with capecitabine)
• Bevacizumab
• Capecitabine

Liver directed therapy(for metastasis)

• Radiation
  • Selective Internal Radiation Therapy
  • Peptide Receptor Radionuclide Therapy (PRRT) - cytotoxic doses of radiation are given locally to the site of tumor (also called Radio-embolization sometimes)
• Hepatic artery embolization, chemo-embolization, and infusion. Infusion consists of:
  • Hepatic artery infusion (HIA) - which is the administration of chemotherapeutic agents(high doses of streptozocin and 5-FU) into the hepatic artery. Response rates are 0-100%.
  • Isolated hepatic perfusion (IHP) which gave rise to minimally invasive, percutaneous hepatic perfusion.
• Percutaneous ethanol injection/ Ethanol ablation
• Radiofrequency ablation (RFA)
• Cryoablation