Complications of hyperglycaemia with PI3K–AKT–mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials
| Autor: | Geuna, E, Roda, D, Rafii, S, Jimenez, B, Capelan, M, Rihawi, K, Montemurro, F, Yap, T A, Kaye, S B, De Bono, J S, Molife, L R, Banerji, U |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Blood Glucose Male mTOR inhibitors Adolescent Antineoplastic Agents Severity of Illness Index Young Adult Risk Factors Neoplasms Hyperglycaemia Humans Hypoglycemic Agents Protein Kinase Inhibitors Aged Phosphoinositide-3 Kinase Inhibitors Retrospective Studies Aged 80 and over Clinical Trials Phase I as Topic metabolic complications TOR Serine-Threonine Kinases AKT inhibitors PI3K inhibitors Middle Aged Case-Control Studies Hyperglycemia Clinical Study PI3K–AKT–mTOR pathway Female Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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