dc.contributor.author | Geuna, E | |
dc.contributor.author | Roda, D | |
dc.contributor.author | Rafii, S | |
dc.contributor.author | Jimenez, B | |
dc.contributor.author | Capelan, M | |
dc.contributor.author | Rihawi, K | |
dc.contributor.author | Montemurro, F | |
dc.contributor.author | Yap, TA | |
dc.contributor.author | Kaye, SB | |
dc.contributor.author | De Bono, JS | |
dc.contributor.author | Molife, LR | |
dc.contributor.author | Banerji, U | |
dc.date.accessioned | 2016-11-23T14:13:13Z | |
dc.date.issued | 2015-12-01 | |
dc.identifier.citation | British journal of cancer, 2015, 113 (11), pp. 1541 - 1547 | |
dc.identifier.issn | 0007-0920 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/261 | |
dc.identifier.eissn | 1532-1827 | |
dc.identifier.doi | 10.1038/bjc.2015.373 | |
dc.description.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<0.001). All patients with high-grade hyperglycaemia received antihyperglycemic treatment and none developed severe metabolic complications (diabetic ketoacidosis or hyperosmolar hyperglycemic nonketotic state). High-grade hyperglycaemia was the cause of permanent PAMi discontinuation in nine patients. CONCLUSIONS: PI3K-AKT-mTOR inhibitors are associated with small (6.7%) but statistically significant increased risk of high-grade hyperglycaemia compared with non-PAM targeting agents. However, PAMi-induced hyperglycaemia was not found to be associated with severe metabolic complications in this non-diabetic population of patients with advanced cancers. | |
dc.format | Print-Electronic | |
dc.format.extent | 1541 - 1547 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Hyperglycemia | |
dc.subject | Blood Glucose | |
dc.subject | Antineoplastic Agents | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Hypoglycemic Agents | |
dc.subject | Severity of Illness Index | |
dc.subject | Risk Factors | |
dc.subject | Case-Control Studies | |
dc.subject | Retrospective Studies | |
dc.subject | Signal Transduction | |
dc.subject | Adolescent | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | Proto-Oncogene Proteins c-akt | |
dc.subject | Clinical Trials, Phase I as Topic | |
dc.subject | Young Adult | |
dc.subject | TOR Serine-Threonine Kinases | |
dc.subject | Phosphoinositide-3 Kinase Inhibitors | |
dc.title | Complications of hyperglycaemia with PI3K-AKT-mTOR inhibitors in patients with advanced solid tumours on Phase I clinical trials. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-10-05 | |
rioxxterms.versionofrecord | 10.1038/bjc.2015.373 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-12 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | British journal of cancer | |
pubs.issue | 11 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye) | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Medicine Drug Development Unit (de Bono) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Pharmacology – Adaptive Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Medicine Drug Development Unit (de Bono) | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Prostate Cancer Targeted Therapy Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/Medicine Drug Development Unit (Kaye) | |
pubs.publication-status | Published | |
pubs.volume | 113 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Pharmacology – Adaptive Therapy | |
icr.researchteam | Medicine Drug Development Unit (de Bono) | |
icr.researchteam | Prostate Cancer Targeted Therapy Group | |
icr.researchteam | Medicine Drug Development Unit (Kaye) | |
dc.contributor.icrauthor | De Bono, Johann | |
dc.contributor.icrauthor | Banerji, Udai | |