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10.1093/neuonc/nou208.15 http://scihub22266oqcxt.onion/10.1093/neuonc/nou208.15 C4144559/?report=reader!4144559!C4144559     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 298.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 332.4 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Neuro+Oncol 2014 ; 16 (Suppl 3): iii27 Nephropedia Template TP {{tp|p=C4144559|t=2014. FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA A POETIC CONSORTIUM TRIAL |pdf=|usr=}}{{C4144559}} gab.com Text FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA A POETIC CONSORTIUM TRIAL JO: Neuro Oncol http://www.kidney.de/pget.php?&tw=1&pmid=C4144559 #FOAvip BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant ras/raf signaling is involved in tumorigenesis through promotion of cell proliferation, survival, and differentiation in sporadic LGG. Everolimus (RAD001) is a potent and selective inhibitor of mTOR, a downstream element of the ras/raf pathway. The activity, safety and pharmacokinetics of everolimus in pediatric patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric patients with radiographic progressive or recurrent LGGs without neurofibromatosis type I were treated with oral everolimus 5mg/m2/dose once daily. Therapy was provided for 28 days (one cycle) and could be repeated for a total of 12 cycles. Response, as determined by standard 2-D MRI criteria, was assessed for all patients. Pharmacokinetics, pharmacogenetics, pharmacodynamic parameters including inhibition of p70s6 kinase activity, 4E-BP1 phosphorylation inhibition and suppression of cMyc expression, as well as the toxicity profile of everolimus were evaluated. RESULTS: Twenty-three patients with a median age of 9 years (range, 3?17 years) were enrolled, all of whom had received prior chemotherapy (average # regimens = 2.7) including progression after a carboplatin-containing regimen. Median number of cycles of therapy was 10 (range, 1-12). Responses were determined by blinded central review and included 4 patients with PR (>50% decrease) and 13 with stable disease. Six patients had progressive disease by one year. Overall therapy was well tolerated; two patients discontinued therapy due to mouth sores (n = 1) and withdrawal of consent (n = 1). Everolimus PK parameters were similar to those previously reported in both adult and pediatric patients and drug trough levels were maintained above 5ng/ml. Pharmacodynamic analysis demonstrated inhibition of downstream targets of mTOR including phospho-S6 kinase, 4E-BP1 phosphorylation and cMyc expression within 14 days of initiation of everolimus therapy and this inhibition was maintained throughout the treatment period. CONCLUSIONS: Everolimus was well tolerated in pediatric patients with progressive or recurrent LGGs and demonstrated activity in this multiply recurrent/progressive patient population. Incorporation of everolimus into frontline LGG therapy is being proposed. SECONDARY CATEGORY: Clinical Neuro-Oncology. Twit Text FOAVip FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA A POETIC CONSORTIUM TRIAL ????Neuro Oncol http://www.kidney.de/pget.php?&tw=1&pmid=C4144559 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=C4144559 #FOAvip English Wikipedia <ref>{{Cite pmid|C4144559}}</ref> FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA A POETIC CONSORTIUM TRIAL #MMPMIDC4144559 Kieran MW; Yao X; Macy M; Leary S; Cohen K; MacDonald T; Allen J; Boklan J; Smith A; Nazemi K; Gore L; Trippett T; DiRenzo J; Narendran A; Perentesis J; Prabhu S; Pinches N; Robison N; Manley P; Chi S Neuro Oncol 2014[Jul]; 16 (Suppl 3): iii27 PMIDC4144559show ga BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant ras/raf signaling is involved in tumorigenesis through promotion of cell proliferation, survival, and differentiation in sporadic LGG. Everolimus (RAD001) is a potent and selective inhibitor of mTOR, a downstream element of the ras/raf pathway. The activity, safety and pharmacokinetics of everolimus in pediatric patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric patients with radiographic progressive or recurrent LGGs without neurofibromatosis type I were treated with oral everolimus 5mg/m2/dose once daily. Therapy was provided for 28 days (one cycle) and could be repeated for a total of 12 cycles. Response, as determined by standard 2-D MRI criteria, was assessed for all patients. Pharmacokinetics, pharmacogenetics, pharmacodynamic parameters including inhibition of p70s6 kinase activity, 4E-BP1 phosphorylation inhibition and suppression of cMyc expression, as well as the toxicity profile of everolimus were evaluated. RESULTS: Twenty-three patients with a median age of 9 years (range, 3?17 years) were enrolled, all of whom had received prior chemotherapy (average # regimens = 2.7) including progression after a carboplatin-containing regimen. Median number of cycles of therapy was 10 (range, 1-12). Responses were determined by blinded central review and included 4 patients with PR (>50% decrease) and 13 with stable disease. Six patients had progressive disease by one year. Overall therapy was well tolerated; two patients discontinued therapy due to mouth sores (n = 1) and withdrawal of consent (n = 1). Everolimus PK parameters were similar to those previously reported in both adult and pediatric patients and drug trough levels were maintained above 5ng/ml. Pharmacodynamic analysis demonstrated inhibition of downstream targets of mTOR including phospho-S6 kinase, 4E-BP1 phosphorylation and cMyc expression within 14 days of initiation of everolimus therapy and this inhibition was maintained throughout the treatment period. CONCLUSIONS: Everolimus was well tolerated in pediatric patients with progressive or recurrent LGGs and demonstrated activity in this multiply recurrent/progressive patient population. Incorporation of everolimus into frontline LGG therapy is being proposed. SECONDARY CATEGORY: Clinical Neuro-Oncology. äFINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF E(epmc).pdf DeepDyve Pubget Overpricing