Efficacy of everolimus in patients with metastatic insulinoma and refractory hypoglycemia

Eur J Endocrinol. 2013 Apr 15;168(5):665-74. doi: 10.1530/EJE-12-1101. Print 2013 May.

Abstract

Background: Refractory hypoglycemia in patients with metastatic insulinoma is an important cause of morbidity and mortality. Everolimus could be a new therapeutic option.

Methods: Within the French Group, we conducted a retrospective, multicentric study of endocrine tumors to evaluate the time to the first recurrence of symptomatic hypoglycemia, after everolimus initiation, in patients with metastatic insulinoma and refractory hypoglycemia. Ongoing hyperglycemic medical options, tumor response, and safety information were recorded.

Results: Twelve patients with metastatic insulinoma and refractory hypoglycemia who were treated with everolimus between May 2007 and June 2011 were reviewed. Everolimus (starting dose, 10 mg/day, except in one patient, 5 mg/day) was given after a median of four previous therapeutic lines. Medication aimed at normalizing blood glucose levels in 11 patients. After a median duration of 6.5 months (range 1-35+ months), median time to the first recurrence of symptomatic hypoglycemia was 6.5 months (range 0 to 35+ months). Three patients discontinued everolimus because of cardiac and/or pulmonary adverse events at 1, 1.5, and 7 months after initiation, which led to two deaths. Three patients discontinued everolimus because of tumor progression at 2, 3, and 10 months after initiation, without recurrence of hypoglycemia.

Conclusion: Everolimus appears to be a new effective treatment for patients with metastatic insulinoma and refractory hypoglycemia. Tolerance should be carefully monitored.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Everolimus
  • Female
  • Humans
  • Hypoglycemia / drug therapy*
  • Hypoglycemia / etiology
  • Insulinoma / complications
  • Insulinoma / drug therapy*
  • Insulinoma / secondary
  • Liver Neoplasms / complications
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / secondary
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / complications
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Retrospective Studies
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Everolimus
  • Sirolimus