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10.1158/1078-0432.CCR-14-2424 http://scihub22266oqcxt.onion/10.1158/1078-0432.CCR-14-2424 C4401558!4401558 !25649020     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25649020 &cmd=llinks): Failed to open stream: HTTP request failed! 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Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials |pdf=|usr=}}{{25649020 }} gab.com Text Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials JO: Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25649020 #FOAvip 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. Twit Text FOAVip Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials ????Clin Cancer Res http://www.kidney.de/pget.php?&tw=1&pmid=25649020 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25649020 #FOAvip English Wikipedia <ref>{{Cite pmid|25649020 }}</ref> Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials #MMPMID25649020 Rafii S ; Roda D ; Geuna E ; Jimenez B ; Rihawi K ; Capelan M ; Yap TA ; Molife LR ; Kaye SB ; de Bono JS ; Banerji U Clin Cancer Res 2015[Apr]; 21 (8 ): 1869-76 PMID25649020 show ga 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. |Adolescent [MESH] |Adult [MESH] |Aged [MESH] |Aged, 80 and over [MESH] |Antineoplastic Agents/adverse effects/*therapeutic use [MESH] |Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use [MESH] |Biomarkers [MESH] |Case-Control Studies [MESH] |Clinical Trials, Phase I as Topic [MESH] |Female [MESH] |Humans [MESH] |Incidence [MESH] |Infections/*epidemiology/*etiology [MESH] |Male [MESH] |Middle Aged [MESH] |Neoplasm Metastasis [MESH] |Neoplasm Staging [MESH] |Neoplasms/*complications/diagnosis/*drug therapy/metabolism [MESH] |Phosphoinositide-3 Kinase Inhibitors [MESH] |Protein Kinase Inhibitors/adverse effects/*therapeutic use [MESH] |Proto-Oncogene Proteins c-akt/antagonists & inhibitors [MESH] |Retrospective Studies [MESH] |Risk [MESH] |Signal Transduction/drug effects [MESH] |TOR Serine-Threonine Kinases/antagonists & inhibitors [MESH]Higher Risk of Infections with PI3K-AKT-mTOR Pathway Inhibitors in Pat(epmc).pdf DeepDyve Pubget Overpricing