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10.1007/s10637-014-0199-x http://scihub22266oqcxt.onion/10.1007/s10637-014-0199-x C4390470!4390470 !25556680     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 300.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\25556680 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Invest+New+Drugs 2015 ; 33 (2 ): 397-408 Nephropedia Template TP {{tp|p=25556680 |t=2015. Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer |pdf=|usr=}}{{25556680 }} gab.com Text Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer JO: Invest New Drugs http://www.kidney.de/pget.php?&tw=1&pmid=25556680 #FOAvip BACKGROUND: Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC patients. METHODS: Adult men with chemotherapy-naïve mCRPC, serum prostate-specific antigen (PSA) ?5 ng/mL, and serum testosterone <50 ng/dL received oral orteronel 200 or 400 mg twice-daily (BID) in phase 1 to determine the recommended dose for phase 2, plus intravenous docetaxel 75 mg/m(2) every 3 weeks, and oral prednisone 5 mg BID. Phase 2 objectives included safety, pharmacokinetics, and efficacy. RESULTS: In phase 1 (n?=?6, orteronel 200 mg; n?=?8, orteronel 400 mg), there was one dose-limiting toxicity of grade 3 febrile neutropenia at 400 mg BID. This dose was evaluated further in phase 2 (n?=?23). After 4 cycles, 68, 59, and 23% of patients achieved ?30, ?50, and ?90% PSA reductions, respectively; median best PSA response was -77%. Seven of 10 (70%) RECIST-evaluable patients achieved objective partial responses. Median time to PSA progression and radiographic disease progression was 6.7 and 12.9 months, respectively. Dehydroepiandrosterone-sulfate (DHEA-S) and testosterone levels were rapidly and durably reduced. Common adverse events were fatigue (78%), alopecia (61%), diarrhea (48%), nausea (43%), dysgeusia (39%), and neutropenia (39%). Orteronel and docetaxel pharmacokinetics were similar alone and in combination. CONCLUSIONS: Orteronel plus DP was tolerable, with substantial reductions in PSA, DHEA-S, and testosterone levels, and evidence for measurable disease responses. Twit Text FOAVip Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer ????Invest New Drugs http://www.kidney.de/pget.php?&tw=1&pmid=25556680 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25556680 #FOAvip English Wikipedia <ref>{{Cite pmid|25556680 }}</ref> Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer #MMPMID25556680 Petrylak DP ; Gandhi JG ; Clark WR ; Heath E ; Lin J ; Oh WK ; Agus DB ; Carthon B ; Moran S ; Kong N ; Suri A ; Bargfrede M ; Liu G Invest New Drugs 2015[Apr]; 33 (2 ): 397-408 PMID25556680 show ga BACKGROUND: Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC patients. METHODS: Adult men with chemotherapy-naïve mCRPC, serum prostate-specific antigen (PSA) ?5 ng/mL, and serum testosterone <50 ng/dL received oral orteronel 200 or 400 mg twice-daily (BID) in phase 1 to determine the recommended dose for phase 2, plus intravenous docetaxel 75 mg/m(2) every 3 weeks, and oral prednisone 5 mg BID. Phase 2 objectives included safety, pharmacokinetics, and efficacy. RESULTS: In phase 1 (n?=?6, orteronel 200 mg; n?=?8, orteronel 400 mg), there was one dose-limiting toxicity of grade 3 febrile neutropenia at 400 mg BID. This dose was evaluated further in phase 2 (n?=?23). After 4 cycles, 68, 59, and 23% of patients achieved ?30, ?50, and ?90% PSA reductions, respectively; median best PSA response was -77%. Seven of 10 (70%) RECIST-evaluable patients achieved objective partial responses. Median time to PSA progression and radiographic disease progression was 6.7 and 12.9 months, respectively. Dehydroepiandrosterone-sulfate (DHEA-S) and testosterone levels were rapidly and durably reduced. Common adverse events were fatigue (78%), alopecia (61%), diarrhea (48%), nausea (43%), dysgeusia (39%), and neutropenia (39%). Orteronel and docetaxel pharmacokinetics were similar alone and in combination. CONCLUSIONS: Orteronel plus DP was tolerable, with substantial reductions in PSA, DHEA-S, and testosterone levels, and evidence for measurable disease responses. |Aged [MESH] |Aged, 80 and over [MESH] |Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use [MESH] |Antineoplastic Combined Chemotherapy Protocols [MESH] |Dehydroepiandrosterone Sulfate/blood [MESH] |Disease Progression [MESH] |Disease-Free Survival [MESH] |Docetaxel [MESH] |Dose-Response Relationship, Drug [MESH] |Humans [MESH] |Imidazoles/administration & dosage/adverse effects/*therapeutic use [MESH] |Male [MESH] |Middle Aged [MESH] |Naphthalenes/administration & dosage/adverse effects/*therapeutic use [MESH] |Prednisone/administration & dosage/*therapeutic use [MESH] |Prostate-Specific Antigen [MESH] |Prostatic Neoplasms, Castration-Resistant/drug therapy [MESH] |Steroid 17-alpha-Hydroxylase/antagonists & inhibitors [MESH] |Taxoids/administration & dosage/*therapeutic use [MESH]Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase(epmc).pdf DeepDyve Pubget Overpricing