A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer
Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin...
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| Veröffentlicht in: | JNCI : Journal of the National Cancer Institute 2005-09, Vol.97 (17), p.1287-1296 |
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| container_title | JNCI : Journal of the National Cancer Institute |
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| creator | Chi, Kim N. Eisenhauer, Elizabeth Fazli, Ladan Jones, Edward C. Goldenberg, S. Larry Powers, Jean Tu, Dongsheng Gleave, Martin E. |
| description | Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. Methods: Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8–29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30–36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and the pharmacokinetics of OGX-011 were determined from these data. Prostate cancer tissue, lymph nodes, and serial samples of peripheral blood mononuclear cells were assessed for clusterin expression using quantitative real-time polymerase chain reaction and immunohistochemistry. All statistical tests were two-sided. Results: Only grade 1 and 2 toxicities were observed. The plasma half-life of OGX-011 was approximately 2–3 hours, and the area under the concentration versus time curve and CMAX (peak plasma concentration) increased proportionally with dose (Ptrend |
| doi_str_mv | 10.1093/jnci/dji252 |
| format | Article |
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Larry ; Powers, Jean ; Tu, Dongsheng ; Gleave, Martin E.</creator><creatorcontrib>Chi, Kim N. ; Eisenhauer, Elizabeth ; Fazli, Ladan ; Jones, Edward C. ; Goldenberg, S. Larry ; Powers, Jean ; Tu, Dongsheng ; Gleave, Martin E.</creatorcontrib><description>Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. Methods: Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8–29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30–36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and the pharmacokinetics of OGX-011 were determined from these data. Prostate cancer tissue, lymph nodes, and serial samples of peripheral blood mononuclear cells were assessed for clusterin expression using quantitative real-time polymerase chain reaction and immunohistochemistry. All statistical tests were two-sided. Results: Only grade 1 and 2 toxicities were observed. The plasma half-life of OGX-011 was approximately 2–3 hours, and the area under the concentration versus time curve and CMAX (peak plasma concentration) increased proportionally with dose (Ptrend<.001). OGX-011 in prostate tissue increased with dose (Ptrend<.001). Dose-dependent decreases in prostate cancer and lymph node clusterin expression were observed by polymerase chain reaction of greater than 90% (Ptrend = .008 and Ptrend<.001, respectively) and by immunohistochemistry (Ptrend<.001 and Ptrend = .01, respectively). Conclusions: OGX-011 is well tolerated and reduces clusterin expression in primary prostate tumors. The optimal biologic dose for OGX-011 at the schedule used is 640 mg.</description><identifier>ISSN: 0027-8874</identifier><identifier>EISSN: 1460-2105</identifier><identifier>DOI: 10.1093/jnci/dji252</identifier><identifier>PMID: 16145049</identifier><identifier>CODEN: JNCIEQ</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject><![CDATA[Aged ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - pharmacokinetics ; Antineoplastic Agents - pharmacology ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - pharmacology ; Apoptosis - drug effects ; Biological and medical sciences ; Chemotherapy, Adjuvant ; Clusterin ; Complement Inactivator Proteins - antagonists & inhibitors ; Complement Inactivator Proteins - metabolism ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug therapy ; Enzyme-Linked Immunosorbent Assay ; Gene Expression Regulation, Neoplastic - drug effects ; Glycoproteins - antagonists & inhibitors ; Glycoproteins - metabolism ; Half-Life ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Infusions, Intravenous ; Lymph Nodes - drug effects ; Lymph Nodes - metabolism ; Male ; Medical research ; Medical sciences ; Middle Aged ; Molecular Chaperones - antagonists & inhibitors ; Molecular Chaperones - metabolism ; Neoadjuvant Therapy ; Neoplasm Staging ; Oligonucleotides, Antisense - administration & dosage ; Oligonucleotides, Antisense - adverse effects ; Oligonucleotides, Antisense - pharmacology ; Pharmacology ; Polymerase Chain Reaction ; Prostate cancer ; Prostatectomy ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - surgery ; Proteins ; Thionucleotides - administration & dosage ; Thionucleotides - pharmacokinetics ; Thionucleotides - pharmacology ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tumors]]></subject><ispartof>JNCI : Journal of the National Cancer Institute, 2005-09, Vol.97 (17), p.1287-1296</ispartof><rights>2005 INIST-CNRS</rights><rights>Copyright Oxford University Press(England) Sep 7, 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c450t-6d74378b4924f8e7a73adb8df8ff69408a9f7acb118955d03d6c32b89f89a3c3</citedby><cites>FETCH-LOGICAL-c450t-6d74378b4924f8e7a73adb8df8ff69408a9f7acb118955d03d6c32b89f89a3c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17108755$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16145049$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chi, Kim N.</creatorcontrib><creatorcontrib>Eisenhauer, Elizabeth</creatorcontrib><creatorcontrib>Fazli, Ladan</creatorcontrib><creatorcontrib>Jones, Edward C.</creatorcontrib><creatorcontrib>Goldenberg, S. Larry</creatorcontrib><creatorcontrib>Powers, Jean</creatorcontrib><creatorcontrib>Tu, Dongsheng</creatorcontrib><creatorcontrib>Gleave, Martin E.</creatorcontrib><title>A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer</title><title>JNCI : Journal of the National Cancer Institute</title><addtitle>JNCI J Natl Cancer Inst</addtitle><description>Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. Methods: Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8–29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30–36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and the pharmacokinetics of OGX-011 were determined from these data. Prostate cancer tissue, lymph nodes, and serial samples of peripheral blood mononuclear cells were assessed for clusterin expression using quantitative real-time polymerase chain reaction and immunohistochemistry. All statistical tests were two-sided. Results: Only grade 1 and 2 toxicities were observed. The plasma half-life of OGX-011 was approximately 2–3 hours, and the area under the concentration versus time curve and CMAX (peak plasma concentration) increased proportionally with dose (Ptrend<.001). OGX-011 in prostate tissue increased with dose (Ptrend<.001). Dose-dependent decreases in prostate cancer and lymph node clusterin expression were observed by polymerase chain reaction of greater than 90% (Ptrend = .008 and Ptrend<.001, respectively) and by immunohistochemistry (Ptrend<.001 and Ptrend = .01, respectively). Conclusions: OGX-011 is well tolerated and reduces clusterin expression in primary prostate tumors. The optimal biologic dose for OGX-011 at the schedule used is 640 mg.</description><subject>Aged</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Biological and medical sciences</subject><subject>Chemotherapy, Adjuvant</subject><subject>Clusterin</subject><subject>Complement Inactivator Proteins - antagonists & inhibitors</subject><subject>Complement Inactivator Proteins - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Administration Schedule</subject><subject>Drug therapy</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Glycoproteins - antagonists & inhibitors</subject><subject>Glycoproteins - metabolism</subject><subject>Half-Life</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Infusions, Intravenous</subject><subject>Lymph Nodes - drug effects</subject><subject>Lymph Nodes - metabolism</subject><subject>Male</subject><subject>Medical research</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Molecular Chaperones - antagonists & inhibitors</subject><subject>Molecular Chaperones - metabolism</subject><subject>Neoadjuvant Therapy</subject><subject>Neoplasm Staging</subject><subject>Oligonucleotides, Antisense - administration & dosage</subject><subject>Oligonucleotides, Antisense - adverse effects</subject><subject>Oligonucleotides, Antisense - pharmacology</subject><subject>Pharmacology</subject><subject>Polymerase Chain Reaction</subject><subject>Prostate cancer</subject><subject>Prostatectomy</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - surgery</subject><subject>Proteins</subject><subject>Thionucleotides - administration & dosage</subject><subject>Thionucleotides - pharmacokinetics</subject><subject>Thionucleotides - pharmacology</subject><subject>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</subject><subject>Tumors</subject><issn>0027-8874</issn><issn>1460-2105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkd9qFDEUxgdR7LZ65b0EQW_s2CTzJ8nlOtRuYXULFl28CZkk42Y7k9QkAx2vfBofwEfyScyySwvmIgdOfnwn5_uy7AWC7xBkxdnWSnOmtgZX-FE2Q2UNc4xg9TibQYhJTikpj7LjELYwHYbLp9kRqlFZwZLNst9zcLURQYPLXfWDkO7GWB2NBMKq-56arBhS73Mc1QRcB1YX6xwidAoEwH9__ck_6rhxd1O6px7MbTRB26S66s13Z0fZaxeN0iA60PRjiNobewqMBVciGm1jAF9N3IClk6I3P3Ua7F2IImrQCCu1f5Y96UQf9PNDPcmuP5xfN4t8ubq4bObLXKZ9Yl4rUhaEtmVas6OaCFII1VLV0a6rWQmpYB0RskWIsqpSsFC1LHBLWUeZKGRxkr3Zy95692PUIfLBBKn7XljtxsAx3MkTlsBX_4FbN3qbvsZxMr_AjNQJeruHZFomeN3xW28G4SeOIN9Fx3fR8X10iX55kBzbQasH9pBVAl4fABGSTZ1PzpjwwBEEKamqxOV7ziSf7-7fhb_hNSlIxRfrb3y9wPTT--YLR8U_PvCzhg</recordid><startdate>20050907</startdate><enddate>20050907</enddate><creator>Chi, Kim N.</creator><creator>Eisenhauer, Elizabeth</creator><creator>Fazli, Ladan</creator><creator>Jones, Edward C.</creator><creator>Goldenberg, S. Larry</creator><creator>Powers, Jean</creator><creator>Tu, Dongsheng</creator><creator>Gleave, Martin E.</creator><general>Oxford University Press</general><general>Oxford Publishing Limited (England)</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7QO</scope><scope>7T2</scope><scope>7U1</scope><scope>7U2</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20050907</creationdate><title>A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer</title><author>Chi, Kim N. ; Eisenhauer, Elizabeth ; Fazli, Ladan ; Jones, Edward C. ; Goldenberg, S. Larry ; Powers, Jean ; Tu, Dongsheng ; Gleave, Martin E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c450t-6d74378b4924f8e7a73adb8df8ff69408a9f7acb118955d03d6c32b89f89a3c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aged</topic><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Biological and medical sciences</topic><topic>Chemotherapy, Adjuvant</topic><topic>Clusterin</topic><topic>Complement Inactivator Proteins - antagonists & inhibitors</topic><topic>Complement Inactivator Proteins - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Administration Schedule</topic><topic>Drug therapy</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Glycoproteins - antagonists & inhibitors</topic><topic>Glycoproteins - metabolism</topic><topic>Half-Life</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization</topic><topic>Infusions, Intravenous</topic><topic>Lymph Nodes - drug effects</topic><topic>Lymph Nodes - metabolism</topic><topic>Male</topic><topic>Medical research</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Molecular Chaperones - antagonists & inhibitors</topic><topic>Molecular Chaperones - metabolism</topic><topic>Neoadjuvant Therapy</topic><topic>Neoplasm Staging</topic><topic>Oligonucleotides, Antisense - administration & dosage</topic><topic>Oligonucleotides, Antisense - adverse effects</topic><topic>Oligonucleotides, Antisense - pharmacology</topic><topic>Pharmacology</topic><topic>Polymerase Chain Reaction</topic><topic>Prostate cancer</topic><topic>Prostatectomy</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - surgery</topic><topic>Proteins</topic><topic>Thionucleotides - administration & dosage</topic><topic>Thionucleotides - pharmacokinetics</topic><topic>Thionucleotides - pharmacology</topic><topic>Transfusions. Complications. Transfusion reactions. Cell and gene therapy</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chi, Kim N.</creatorcontrib><creatorcontrib>Eisenhauer, Elizabeth</creatorcontrib><creatorcontrib>Fazli, Ladan</creatorcontrib><creatorcontrib>Jones, Edward C.</creatorcontrib><creatorcontrib>Goldenberg, S. Larry</creatorcontrib><creatorcontrib>Powers, Jean</creatorcontrib><creatorcontrib>Tu, Dongsheng</creatorcontrib><creatorcontrib>Gleave, Martin E.</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology Research Abstracts</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>JNCI : Journal of the National Cancer Institute</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chi, Kim N.</au><au>Eisenhauer, Elizabeth</au><au>Fazli, Ladan</au><au>Jones, Edward C.</au><au>Goldenberg, S. Larry</au><au>Powers, Jean</au><au>Tu, Dongsheng</au><au>Gleave, Martin E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer</atitle><jtitle>JNCI : Journal of the National Cancer Institute</jtitle><addtitle>JNCI J Natl Cancer Inst</addtitle><date>2005-09-07</date><risdate>2005</risdate><volume>97</volume><issue>17</issue><spage>1287</spage><epage>1296</epage><pages>1287-1296</pages><issn>0027-8874</issn><eissn>1460-2105</eissn><coden>JNCIEQ</coden><abstract>Background: Clusterin is a cytoprotective chaperone protein that promotes cell survival and confers broad-spectrum treatment resistance. OGX-011 is a 2′-methoxyethyl modified phosphorothioate antisense oligonucleotide that is complementary to clusterin mRNA and has been reported to inhibit clusterin expression and enhance drug efficacy in xenograft models. The primary objective of this clinical study was to determine a biologically effective dose of OGX-011 that would inhibit clusterin expression in human cancer. Methods: Subjects (n = 25) with localized prostate cancer with high-risk features who were candidates for prostatectomy were treated with OGX-011 by 2-hour intravenous infusion on days 1, 3, and 5 and then weekly from days 8–29 combined with androgen blockade starting on day 1; prostatectomy was performed on days 30–36. Six different doses were tested, from 40 to 640 mg. OGX-011 plasma and prostate tissue concentrations were measured by an enzyme-linked immunosorbent assay method, and the pharmacokinetics of OGX-011 were determined from these data. Prostate cancer tissue, lymph nodes, and serial samples of peripheral blood mononuclear cells were assessed for clusterin expression using quantitative real-time polymerase chain reaction and immunohistochemistry. All statistical tests were two-sided. Results: Only grade 1 and 2 toxicities were observed. The plasma half-life of OGX-011 was approximately 2–3 hours, and the area under the concentration versus time curve and CMAX (peak plasma concentration) increased proportionally with dose (Ptrend<.001). OGX-011 in prostate tissue increased with dose (Ptrend<.001). Dose-dependent decreases in prostate cancer and lymph node clusterin expression were observed by polymerase chain reaction of greater than 90% (Ptrend = .008 and Ptrend<.001, respectively) and by immunohistochemistry (Ptrend<.001 and Ptrend = .01, respectively). Conclusions: OGX-011 is well tolerated and reduces clusterin expression in primary prostate tumors. The optimal biologic dose for OGX-011 at the schedule used is 640 mg.</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>16145049</pmid><doi>10.1093/jnci/dji252</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | JNCI : Journal of the National Cancer Institute, 2005-09, Vol.97 (17), p.1287-1296 |
| issn | 0027-8874 1460-2105 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Aged Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacokinetics Antineoplastic Agents - pharmacology Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - pharmacology Apoptosis - drug effects Biological and medical sciences Chemotherapy, Adjuvant Clusterin Complement Inactivator Proteins - antagonists & inhibitors Complement Inactivator Proteins - metabolism Dose-Response Relationship, Drug Drug Administration Schedule Drug therapy Enzyme-Linked Immunosorbent Assay Gene Expression Regulation, Neoplastic - drug effects Glycoproteins - antagonists & inhibitors Glycoproteins - metabolism Half-Life Humans Immunohistochemistry In Situ Hybridization Infusions, Intravenous Lymph Nodes - drug effects Lymph Nodes - metabolism Male Medical research Medical sciences Middle Aged Molecular Chaperones - antagonists & inhibitors Molecular Chaperones - metabolism Neoadjuvant Therapy Neoplasm Staging Oligonucleotides, Antisense - administration & dosage Oligonucleotides, Antisense - adverse effects Oligonucleotides, Antisense - pharmacology Pharmacology Polymerase Chain Reaction Prostate cancer Prostatectomy Prostatic Neoplasms - blood Prostatic Neoplasms - drug therapy Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Prostatic Neoplasms - surgery Proteins Thionucleotides - administration & dosage Thionucleotides - pharmacokinetics Thionucleotides - pharmacology Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tumors |
| title | A Phase I Pharmacokinetic and Pharmacodynamic Study of OGX-011, a 2′-Methoxyethyl Antisense Oligonucleotide to Clusterin, in Patients With Localized Prostate Cancer |
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