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 are unable to 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 are unable to 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

• 1.1 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.
• 1.2 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:
  • 2.1.1 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

1. 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

2. Liver-directed therapy (for metastasis)

• 2.1 Radiation
  • 2.1.1 Selective internal radiation therapy
  • 2.1.2 Peptide receptor radionuclide therapy (PRRT): cytotoxic doses of radiation are given locally to the site of tumor (sometimes also called Radio-embolization)
• 2.2 Hepatic artery embolization, chemo-embolization, and infusion. Infusion consists of:
  • 2.2.1 Hepatic artery infusion (HIA): HIA is the administration of chemotherapeutic agents (high doses of streptozocin and 5-FU) into the hepatic artery. Response rates are 0 to 100%.
  • 2.2.2 Isolated hepatic perfusion (IHP): HIP gave rise to minimally invasive, percutaneous hepatic perfusion.
• 2.3 Percutaneous ethanol injection/ Ethanol ablation
• 2.4 Radiofrequency ablation (RFA)
• 2.5 Cryoablation