Risk of Metabolic Complications in Patients with Solid Tumors Treated with mTOR inhibitors: Meta-analysis

Anticancer Res. 2016 Apr;36(4):1711-8.

Abstract

Background/aim: Numerous trials have described a wide variation of metabolic complications associated with the mammalian target of rapamycin inhibitors (mTORi). This analysis aimed to report and critically analyze the risks of mTORi-associated metabolic complications.

Materials and methods: A comprehensive search of all published phase II or III randomized controlled trials were investigated. Outcomes included were adverse effect profiles of hyperglycemia (HGC), hypertriglyceridemia (HTG), and hypercholesterolemia (HCE).

Results: Sixteen phase II/III clinical trials were identified. The overall incidence of all-grade (AG) and high-grade (HG) metabolic complications associated with mTORi were 39.7% and 4.1% respectively. mTORi use was associated with an increased risk of AG (2.97 [2.25-3.92]) and HG HGC (4.08 [2.71-6.14]), AG (2.22 [1.70-2.89]) and HG HTG (1.88 [1.10-3.20]), and AG (2.48 [1.83-3.36]) and HG HCE (4.26 [2.30-7.90]).

Conclusion: mTORi are associated with a significantly increased risk of AG and HG HGC, HTG, and HCE. Clinicians should be aware of these risks, perform regular monitoring, and consider alternative anti-neoplastic treatments or adjunctive pharmacological intervention if necessary.

Keywords: afinitor; everolimus; hypercholesterolemia; hyperglycemia; hypertriglyceridemia; mTOR inhibitor; ridaforolimus; temsirolimus; torisel.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Humans
  • Incidence
  • Metabolic Diseases / chemically induced*
  • Metabolic Diseases / etiology
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Protein Kinase Inhibitors / adverse effects*
  • Protein Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • Young Adult

Substances

  • Protein Kinase Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases