Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials

E. Geuna, D. Roda, S. Rafii, B. Jimenez, M. Capelan, K. Rihawi, F. Montemurro, T. A. Yap, S. B. Kaye, J. S. De Bono, L. R. Molife, U. Banerji

Research output: Contribution to journalArticlepeer-review

Abstract

Background:PI3K-AKT-mTOR inhibitors (PAMi) are promising anticancer treatments. Hyperglycaemia is a mechanism-based toxicity of these agents and is becoming increasingly important with their use in larger numbers of patients.Methods:Retrospective case-control study comparing incidence and severity of hyperglycaemia (all grades) between a case group of 387 patients treated on 18 phase I clinical trials with PAMi (78 patients with PI3Ki, 138 with mTORi, 144 with AKTi and 27 with PI3K/mTORi) and a control group of 109 patients treated on 10 phase I clinical trials with agents not directly targeting the PAM pathway. Diabetic patients were excluded in both groups.Results:The incidence of hyperglycaemia was not significantly different between cases and controls (86.6% vs 80.7%, respectively, P=0.129). However, high grade (grade 3-4) hyperglycaemia was more frequent in the PAMi group than in controls (6.7% vs 0%, respectively, P=0.005). The incidence of grade 3-4 hyperglycaemia was greater with AKT and multikinase inhibitors compared with other PAMi (P

Original languageEnglish
Pages (from-to)1541-1547
Number of pages7
JournalBritish Journal of Cancer
Volume113
Issue number11
DOIs
Publication statusPublished - Dec 1 2015

Keywords

  • AKT inhibitors
  • Hyperglycaemia
  • metabolic complications
  • mTOR inhibitors
  • PI3K inhibitors
  • PI3K-AKT-mTOR pathway

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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