Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development
We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrati...
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| Veröffentlicht in: | Pharmaceutical research 2006-06, Vol.23 (6), p.1265-1274 |
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| creator | Chen, Danny Song, Sae Heum Wientjes, M Guillaume Yeh, Teng Kuang Zhao, Liang Villalona-Calero, Miguel Otterson, Gregory A Jensen, Rhonda Grever, Michael Murgo, Anthony J Au, Jessie L-S |
| description | We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrations over 48 h.
Nonsmall cell lung cancer patients were given suramin, paclitaxel, and carboplatin, every 3 weeks. The starting chemosensitizing suramin dose was estimated based on previous results on MTD suramin in patients, and adjusted by using real-time pharmacokinetic monitoring. A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles).
The chemosensitizing suramin dose showed a terminal half-life of 202 h and a total body clearance of 0.029 L h(-1) m(-2) (higher than the 0.013 L h(-1) m(-2) value for MTD of suramin). The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments.
The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models. |
| doi_str_mv | 10.1007/s11095-006-0165-1 |
| format | Article |
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Nonsmall cell lung cancer patients were given suramin, paclitaxel, and carboplatin, every 3 weeks. The starting chemosensitizing suramin dose was estimated based on previous results on MTD suramin in patients, and adjusted by using real-time pharmacokinetic monitoring. A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles).
The chemosensitizing suramin dose showed a terminal half-life of 202 h and a total body clearance of 0.029 L h(-1) m(-2) (higher than the 0.013 L h(-1) m(-2) value for MTD of suramin). The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments.
The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-006-0165-1</identifier><identifier>PMID: 16715360</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Algorithms ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - pharmacokinetics ; Blood Proteins - chemistry ; Blood Proteins - metabolism ; Cancer therapies ; Carboplatin - pharmacokinetics ; Carboplatin - therapeutic use ; Carcinoma, Non-Small-Cell Lung - drug therapy ; Cell cycle ; Chemotherapy ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Drug Administration Schedule ; Drug dosages ; Drug Interactions ; Drug Therapy, Combination ; Female ; Growth factors ; Humans ; Kinases ; Lung cancer ; Lung Neoplasms - drug therapy ; Male ; Models, Biological ; Nomograms ; Paclitaxel - pharmacokinetics ; Paclitaxel - therapeutic use ; Patients ; Pharmacokinetics ; Plasma ; Protein Binding ; Reproducibility of Results ; RNA polymerase ; Suramin - administration & dosage ; Suramin - pharmacokinetics ; Tumors</subject><ispartof>Pharmaceutical research, 2006-06, Vol.23 (6), p.1265-1274</ispartof><rights>Springer Science + Business Media, Inc. 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c326t-da1bb9f5594216e4c3bfd30549edea0595ec1ba9df2aedfda47c7dfc3f3a70eb3</citedby><cites>FETCH-LOGICAL-c326t-da1bb9f5594216e4c3bfd30549edea0595ec1ba9df2aedfda47c7dfc3f3a70eb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16715360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Danny</creatorcontrib><creatorcontrib>Song, Sae Heum</creatorcontrib><creatorcontrib>Wientjes, M Guillaume</creatorcontrib><creatorcontrib>Yeh, Teng Kuang</creatorcontrib><creatorcontrib>Zhao, Liang</creatorcontrib><creatorcontrib>Villalona-Calero, Miguel</creatorcontrib><creatorcontrib>Otterson, Gregory A</creatorcontrib><creatorcontrib>Jensen, Rhonda</creatorcontrib><creatorcontrib>Grever, Michael</creatorcontrib><creatorcontrib>Murgo, Anthony J</creatorcontrib><creatorcontrib>Au, Jessie L-S</creatorcontrib><title>Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrations over 48 h.
Nonsmall cell lung cancer patients were given suramin, paclitaxel, and carboplatin, every 3 weeks. The starting chemosensitizing suramin dose was estimated based on previous results on MTD suramin in patients, and adjusted by using real-time pharmacokinetic monitoring. A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles).
The chemosensitizing suramin dose showed a terminal half-life of 202 h and a total body clearance of 0.029 L h(-1) m(-2) (higher than the 0.013 L h(-1) m(-2) value for MTD of suramin). The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments.
The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models.</description><subject>Algorithms</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - pharmacokinetics</subject><subject>Blood Proteins - chemistry</subject><subject>Blood Proteins - metabolism</subject><subject>Cancer therapies</subject><subject>Carboplatin - pharmacokinetics</subject><subject>Carboplatin - therapeutic use</subject><subject>Carcinoma, Non-Small-Cell Lung - drug therapy</subject><subject>Cell cycle</subject><subject>Chemotherapy</subject><subject>Clinical Trials, Phase I as Topic</subject><subject>Clinical Trials, Phase II as Topic</subject><subject>Drug Administration Schedule</subject><subject>Drug dosages</subject><subject>Drug Interactions</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Kinases</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Male</subject><subject>Models, Biological</subject><subject>Nomograms</subject><subject>Paclitaxel - pharmacokinetics</subject><subject>Paclitaxel - therapeutic use</subject><subject>Patients</subject><subject>Pharmacokinetics</subject><subject>Plasma</subject><subject>Protein Binding</subject><subject>Reproducibility of Results</subject><subject>RNA polymerase</subject><subject>Suramin - administration & dosage</subject><subject>Suramin - pharmacokinetics</subject><subject>Tumors</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpFkE1LxDAQhoMo7rr6A7xI8B6dSZp0603EL1jWi4K3kCbp2mXb1KQV9dfbZRc8Dcy8zzvwEHKOcIUA-XVChEIyAMUAlWR4QKYoc8EKyN4PyRRynrF5nuGEnKS0BoA5FtkxmaDKUQoFU7JchrYP37WlaYimqVtqEjXUfvgmJN-muq9_faTjvjN97ds-3VAXUt2uaBuasBoZ6vyX34SuGa-n5Kgym-TP9nNG3h7uX--e2OLl8fnudsGs4KpnzmBZFpWURcZR-cyKsnICZFZ45w3IQnqLpSlcxY13lTNZbnNXWVEJk4MvxYxc7nq7GD4Hn3q9DkNsx5eac66UVMjHEO5CNoaUoq90F-vGxB-NoLcC9U6gHgXqrUCNI3OxLx7Kxrt_Ym9M_AFiUG3Y</recordid><startdate>200606</startdate><enddate>200606</enddate><creator>Chen, Danny</creator><creator>Song, Sae Heum</creator><creator>Wientjes, M Guillaume</creator><creator>Yeh, Teng Kuang</creator><creator>Zhao, Liang</creator><creator>Villalona-Calero, Miguel</creator><creator>Otterson, Gregory A</creator><creator>Jensen, Rhonda</creator><creator>Grever, Michael</creator><creator>Murgo, Anthony J</creator><creator>Au, Jessie L-S</creator><general>Springer Nature B.V</general><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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>200606</creationdate><title>Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development</title><author>Chen, Danny ; Song, Sae Heum ; Wientjes, M Guillaume ; Yeh, Teng Kuang ; Zhao, Liang ; Villalona-Calero, Miguel ; Otterson, Gregory A ; Jensen, Rhonda ; Grever, Michael ; Murgo, Anthony J ; Au, Jessie L-S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c326t-da1bb9f5594216e4c3bfd30549edea0595ec1ba9df2aedfda47c7dfc3f3a70eb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Algorithms</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - pharmacokinetics</topic><topic>Blood Proteins - chemistry</topic><topic>Blood Proteins - metabolism</topic><topic>Cancer therapies</topic><topic>Carboplatin - pharmacokinetics</topic><topic>Carboplatin - therapeutic use</topic><topic>Carcinoma, Non-Small-Cell Lung - drug therapy</topic><topic>Cell cycle</topic><topic>Chemotherapy</topic><topic>Clinical Trials, Phase I as Topic</topic><topic>Clinical Trials, Phase II as Topic</topic><topic>Drug Administration Schedule</topic><topic>Drug dosages</topic><topic>Drug Interactions</topic><topic>Drug Therapy, Combination</topic><topic>Female</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Kinases</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Male</topic><topic>Models, Biological</topic><topic>Nomograms</topic><topic>Paclitaxel - pharmacokinetics</topic><topic>Paclitaxel - therapeutic use</topic><topic>Patients</topic><topic>Pharmacokinetics</topic><topic>Plasma</topic><topic>Protein Binding</topic><topic>Reproducibility of Results</topic><topic>RNA polymerase</topic><topic>Suramin - administration & dosage</topic><topic>Suramin - pharmacokinetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Danny</creatorcontrib><creatorcontrib>Song, Sae Heum</creatorcontrib><creatorcontrib>Wientjes, M Guillaume</creatorcontrib><creatorcontrib>Yeh, Teng Kuang</creatorcontrib><creatorcontrib>Zhao, Liang</creatorcontrib><creatorcontrib>Villalona-Calero, Miguel</creatorcontrib><creatorcontrib>Otterson, Gregory A</creatorcontrib><creatorcontrib>Jensen, Rhonda</creatorcontrib><creatorcontrib>Grever, Michael</creatorcontrib><creatorcontrib>Murgo, Anthony J</creatorcontrib><creatorcontrib>Au, Jessie L-S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Danny</au><au>Song, Sae Heum</au><au>Wientjes, M Guillaume</au><au>Yeh, Teng Kuang</au><au>Zhao, Liang</au><au>Villalona-Calero, Miguel</au><au>Otterson, Gregory A</au><au>Jensen, Rhonda</au><au>Grever, Michael</au><au>Murgo, Anthony J</au><au>Au, Jessie L-S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2006-06</date><risdate>2006</risdate><volume>23</volume><issue>6</issue><spage>1265</spage><epage>1274</epage><pages>1265-1274</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>We reported that suramin produced chemosensitization at nontoxic doses. This benefit was lost at the approximately 10-fold higher, maximally tolerated doses (MTD). The aim of the current study was to identify in patients the chemosensitizing suramin dose that delivers 10-50 microM plasma concentrations over 48 h.
Nonsmall cell lung cancer patients were given suramin, paclitaxel, and carboplatin, every 3 weeks. The starting chemosensitizing suramin dose was estimated based on previous results on MTD suramin in patients, and adjusted by using real-time pharmacokinetic monitoring. A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles).
The chemosensitizing suramin dose showed a terminal half-life of 202 h and a total body clearance of 0.029 L h(-1) m(-2) (higher than the 0.013 L h(-1) m(-2) value for MTD of suramin). The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments.
The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>16715360</pmid><doi>10.1007/s11095-006-0165-1</doi><tpages>10</tpages></addata></record> |
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| subjects | Algorithms Antineoplastic Agents - administration & dosage Antineoplastic Agents - pharmacokinetics Blood Proteins - chemistry Blood Proteins - metabolism Cancer therapies Carboplatin - pharmacokinetics Carboplatin - therapeutic use Carcinoma, Non-Small-Cell Lung - drug therapy Cell cycle Chemotherapy Clinical Trials, Phase I as Topic Clinical Trials, Phase II as Topic Drug Administration Schedule Drug dosages Drug Interactions Drug Therapy, Combination Female Growth factors Humans Kinases Lung cancer Lung Neoplasms - drug therapy Male Models, Biological Nomograms Paclitaxel - pharmacokinetics Paclitaxel - therapeutic use Patients Pharmacokinetics Plasma Protein Binding Reproducibility of Results RNA polymerase Suramin - administration & dosage Suramin - pharmacokinetics Tumors |
| title | Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development |
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