Metabolic complications with the use of mTOR inhibitors for cancer therapy

Shanthi Sivendran, Neeraj Agarwal, Benjamin A. Gartrell, Jian Ying, Kenneth M. Boucher, Toni K. Choueiri, Guru Sonpavde, William K. Oh, Matthew D. Galsky

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Background: mTOR inhibitors are now approved by regulatory agencies for the treatment of a variety of malignancies. The risk of metabolic complications with these agents is not well characterized. Methods: PubMed was searched for articles published from 2001 until 2011. Eligible studies included prospective randomized trials evaluating temsirolimus, everolimus, and ridaforolimus in patients with all solid tumor malignancies. Sixteen eligible phase II clinical trials and 8 randomized controlled clinical trials were included in a systematic review and meta-analysis and the number of metabolic related AEs (hyperglycemia, hypercholesterolemia, and hypertriglyceridemia) was extracted. Incidence rates and incident rate ratios were calculated. Findings: Twenty-four trials, including 4261 patients, were included in the calculation of the incidence rate. The average incidence rate of all grade metabolic related events was 0.70 (95% CI, 0.47, 0.93). The average incidence rate of serious (grade 3 and 4) metabolic related adverse events was 0.11 (95% CI, 0.08, 0.15). The incidence rate ratio (IRR) of a metabolic adverse event with mTOR inhibitor therapy compared with control was 2.93 (95% CI, 2.33, 3.70) and of serious grade 3 and 4 metabolic adverse events was 4.58 (95% CI, 2.86, 7.34). The IRR of all grade hyperglycemia was 2.95 (95% CI, 2.14, 4.05) and of grade 3-4 hyperglycemia was 5.25 (95% CI, 3.07, 9.00). The IRR of all grade hypertriglyceridemia was 2.49 (95% CI, 1.76, 3.52) and of grade 3-4 hypertriglyceridemia was 2.01 (95% CI, 0.65, 6.27). The IRR of all grade hypercholesterolemia was 3.35 (95% CI, 2.17, 5.18) and of grade 3-4 hypercholesterolemia was 6.51 (95% CI, 1.48, 28.59). These findings suggest a statistically significant increase in the risk of hyperglycemia, hypercholesterolemia (all grades and grade 3 and 4), and all grade hypertriglyceridemia associated with mTOR therapy when compared with control. Interpretation: The risk of all grade and grade 3-4, hyperglycemia, hypercholesterolemia, and hypertriglyceridemia, are increase in patients treated with mTOR inhibitors compared with control.

Original languageEnglish (US)
Pages (from-to)190-196
Number of pages7
JournalCancer Treatment Reviews
Volume40
Issue number1
DOIs
StatePublished - Feb 2014

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Hypertriglyceridemia
Hypercholesterolemia
Incidence
Neoplasms
Therapeutics
Phase II Clinical Trials
PubMed
Meta-Analysis
Randomized Controlled Trials
Prospective Studies

Keywords

  • Adverse events
  • Cancer
  • Everolimus
  • Metabolic
  • MTOR inhibitor
  • Ridaforolimus
  • Temsirolimus

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

Cite this

Sivendran, S., Agarwal, N., Gartrell, B. A., Ying, J., Boucher, K. M., Choueiri, T. K., ... Galsky, M. D. (2014). Metabolic complications with the use of mTOR inhibitors for cancer therapy. Cancer Treatment Reviews, 40(1), 190-196. https://doi.org/10.1016/j.ctrv.2013.04.005

Metabolic complications with the use of mTOR inhibitors for cancer therapy. / Sivendran, Shanthi; Agarwal, Neeraj; Gartrell, Benjamin A.; Ying, Jian; Boucher, Kenneth M.; Choueiri, Toni K.; Sonpavde, Guru; Oh, William K.; Galsky, Matthew D.

In: Cancer Treatment Reviews, Vol. 40, No. 1, 02.2014, p. 190-196.

Research output: Contribution to journalArticle

Sivendran, S, Agarwal, N, Gartrell, BA, Ying, J, Boucher, KM, Choueiri, TK, Sonpavde, G, Oh, WK & Galsky, MD 2014, 'Metabolic complications with the use of mTOR inhibitors for cancer therapy', Cancer Treatment Reviews, vol. 40, no. 1, pp. 190-196. https://doi.org/10.1016/j.ctrv.2013.04.005
Sivendran, Shanthi ; Agarwal, Neeraj ; Gartrell, Benjamin A. ; Ying, Jian ; Boucher, Kenneth M. ; Choueiri, Toni K. ; Sonpavde, Guru ; Oh, William K. ; Galsky, Matthew D. / Metabolic complications with the use of mTOR inhibitors for cancer therapy. In: Cancer Treatment Reviews. 2014 ; Vol. 40, No. 1. pp. 190-196.
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AU - Agarwal, Neeraj

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AU - Ying, Jian

AU - Boucher, Kenneth M.

AU - Choueiri, Toni K.

AU - Sonpavde, Guru

AU - Oh, William K.

AU - Galsky, Matthew D.

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KW - Adverse events

KW - Cancer

KW - Everolimus

KW - Metabolic

KW - MTOR inhibitor

KW - Ridaforolimus

KW - Temsirolimus

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