dc.contributor.author | Rafii, S | |
dc.contributor.author | Roda, D | |
dc.contributor.author | Geuna, E | |
dc.contributor.author | Jimenez, B | |
dc.contributor.author | Rihawi, K | |
dc.contributor.author | Capelan, M | |
dc.contributor.author | Yap, TA | |
dc.contributor.author | Molife, LR | |
dc.contributor.author | Kaye, SB | |
dc.contributor.author | de Bono, JS | |
dc.contributor.author | Banerji, U | |
dc.date.accessioned | 2020-07-28T13:28:27Z | |
dc.date.issued | 2015-04-15 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2015, 21 (8), pp. 1869 - 1876 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3877 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-14-2424 | |
dc.description.abstract | PURPOSE: Novel antitumor therapies against the PI3K-AKT-mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are not known to be myelosuppressive, an increased risk of infection has been reported with rapamycin analogues. However, the risk of infection with new inhibitors of this pathway such as PI3K, AKT, mTORC 1/2, or multikinase inhibitors is unknown. EXPERIMENTAL DESIGN: In this retrospective case-control study, we determined the incidence of infection in a group of 432 patients who were treated on 15 phase I clinical trials involving PI3K-AKT-mTOR pathway inhibitors (cases) versus a group of 100 patients on 10 phase I clinical trials of single agent non-PI3K-AKT-mTOR pathway inhibitors (controls) which did not involve conventional cytotoxic agents. We also collected data from 42 patients who were treated with phase I trials of combinations of PI3K-AKT-mTOR inhibitors and MEK inhibitors and 24 patients with combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapies. RESULTS: The incidence of all grade infection was significantly higher with all single-agent PI3K-AKT-mTOR inhibitors compared with the control group [27% vs. 8%, respectively, OR, 4.26; 95% confidence intervals (CI), 1.9-9.1, P = 0.0001]. The incidence of grade 3 and 4 infection was also significantly higher with PI3K-AKT-mTOR inhibitors compared with the control group (10.3% vs. 3%, OR, 3.74; 95% CI, 1.1-12.4; P = 0.02). Also, the combination of PI3K-AKT-mTOR inhibitors and chemotherapy was associated with a significantly higher incidence of all grade (OR, 4.79; 95% CI, 2.0-11.2; P = 0.0001) and high-grade (OR, 2.87; 95% CI, 1.0-7.6; P = 0.03) infection when compared with single-agent PI3K-AKT-mTOR inhibitors. CONCLUSIONS: Inhibitors of the PI3K-AKT-mTOR pathway can be associated with a higher risk of infection. Combinations of PI3K-AKT-mTOR inhibitors and cytotoxic chemotherapy significantly increase the risk of infection. This should be taken into consideration during the design and conduct of trials involving PI3K-AKT-mTOR pathway inhibitors, particularly when combined with chemotherapy or myelosuppressive agents. | |
dc.format | Print-Electronic | |
dc.format.extent | 1869 - 1876 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Neoplasms | |
dc.subject | Neoplasm Metastasis | |
dc.subject | Antineoplastic Agents | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Neoplasm Staging | |
dc.subject | Incidence | |
dc.subject | Risk | |
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 | Biomarkers | |
dc.subject | Phosphoinositide-3 Kinase Inhibitors | |
dc.subject | Infections | |
dc.title | Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2015-01-28 | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-14-2424 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2015-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 8 | |
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 | 21 | |
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 | |