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Metabolic complications with the use of mTOR inhibitors for cancer therapy

Shanthi Sivendran1, Neeraj Agarwal, Benjamin Gartrell

  • 1Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, PA, United States.

Cancer Treatment Reviews
|May 21, 2013
PubMed
Abstract

Insights

mTOR inhibitors significantly increase the risk of metabolic complications like hyperglycemia and hypercholesterolemia. This study quantifies these adverse events in cancer patients treated with these agents.

Area of Science:

  • Oncology
  • Pharmacology
  • Metabolic Medicine

Background:

  • Mammalian target of rapamycin (mTOR) inhibitors are approved for various cancers.
  • Metabolic complications associated with mTOR inhibitors require further characterization.

Purpose of the Study:

  • To systematically review and meta-analyze the incidence and risk of metabolic adverse events in patients treated with mTOR inhibitors.
  • To quantify the risk of hyperglycemia, hypercholesterolemia, and hypertriglyceridemia associated with mTOR inhibitor therapy.

Main Methods:

  • A systematic review and meta-analysis of prospective randomized trials of temsirolimus, everolimus, and ridaforolimus.
  • Search of PubMed for studies published between 2001 and 2011, including 24 trials with 4261 patients.
  • Extraction and calculation of incidence rates and incidence rate ratios for metabolic adverse events.

Main Results:

  • The overall incidence rate of all-grade metabolic events was 0.70, with serious (grade 3-4) events at 0.11.
  • mTOR inhibitor therapy showed a significantly increased risk for metabolic adverse events (IRR 2.93) and serious events (IRR 4.58).
  • Specific increases in risk were observed for all-grade hyperglycemia (IRR 2.95), grade 3-4 hyperglycemia (IRR 5.25), all-grade hypertriglyceridemia (IRR 2.49), and all-grade hypercholesterolemia (IRR 3.35).

Conclusions:

  • Patients treated with mTOR inhibitors exhibit an increased risk of hyperglycemia, hypercholesterolemia, and hypertriglyceridemia compared to controls.
  • Both all-grade and severe (grade 3-4) metabolic adverse events are more frequent in patients receiving mTOR inhibitors.
  • These findings highlight the importance of monitoring metabolic parameters in patients undergoing mTOR inhibitor therapy.
Keywords:
Adverse eventsCancerEverolimusMetabolicRidaforolimusTemsirolimusmTOR inhibitor

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