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Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma
BackgroundThere is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.ObjectiveWe assessed the activity of sorafenib plus met...
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| Published in: | European journal of endocrinology 2012-03, Vol.166 (3), p.451-458 |
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| creator | Berruti, Alfredo Sperone, Paola Ferrero, Anna Germano, Antonina Ardito, Arianna Priola, Adriano Massimiliano De Francia, Silvia Volante, Marco Daffara, Fulvia Generali, Daniele Leboulleux, Sophie Perotti, Paola Baudin, Eric Papotti, Mauro Terzolo, Massimo |
| description | BackgroundThere is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.ObjectiveWe assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.DesignMulticenter, prospective phase II trial.SettingReferral centers for ACC.MethodsTwenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m2 every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.ResultsTumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose–response and time–response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.ConclusionsDespite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended. |
| doi_str_mv | 10.1530/EJE-11-0918 |
| format | article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_crossref_primary_10_1530_EJE_11_0918</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>22189997</sourcerecordid><originalsourceid>FETCH-LOGICAL-b439t-8716f7c7019571b651835ae9d89f0e229e4a0438deff78483405b7fced1f730b3</originalsourceid><addsrcrecordid>eNp90L9vEzEUwHELgWgoTOzICxM66hf7zvaIqhSCKsEAEtvpnf2sGC6-yHbV5r_HUQpsTPbwef7xZew1iPfQS3G1-bzpADphwTxhK1DadoORP56ylTBCdWpQ8oK9KOWnEND24jm7WK_BWGv1ij183WEhvt3yUu_8kS-B3xP9mo_8gG6OFR9o5pg8L0vGQClOHAsv5Jbkr-ouZt_NMRGvO8p4OPKY2mCNlGrh97HuOPpMaXFLrtHhzB1mF9Oyx5fsWcC50KvH9ZJ9v9l8u_7U3X75uL3-cNtNStraGQ1D0E4LsL2GaejByB7JemODoPXakkKhpPEUgjbKSCX6SQdHHoKWYpKX7N35XJeXUjKF8ZDjHvNxBDGe-o2t3wgwnvo1_easD3fTnvxf-ydYA28fAZb2n5AxuVj-uX6w7Q2yOTi7KS7FnXrE0AL89_LflJiJsw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma</title><source>Oxford Academic Journals (OUP)</source><creator>Berruti, Alfredo ; Sperone, Paola ; Ferrero, Anna ; Germano, Antonina ; Ardito, Arianna ; Priola, Adriano Massimiliano ; De Francia, Silvia ; Volante, Marco ; Daffara, Fulvia ; Generali, Daniele ; Leboulleux, Sophie ; Perotti, Paola ; Baudin, Eric ; Papotti, Mauro ; Terzolo, Massimo</creator><creatorcontrib>Berruti, Alfredo ; Sperone, Paola ; Ferrero, Anna ; Germano, Antonina ; Ardito, Arianna ; Priola, Adriano Massimiliano ; De Francia, Silvia ; Volante, Marco ; Daffara, Fulvia ; Generali, Daniele ; Leboulleux, Sophie ; Perotti, Paola ; Baudin, Eric ; Papotti, Mauro ; Terzolo, Massimo</creatorcontrib><description>BackgroundThere is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.ObjectiveWe assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.DesignMulticenter, prospective phase II trial.SettingReferral centers for ACC.MethodsTwenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m2 every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.ResultsTumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose–response and time–response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.ConclusionsDespite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.</description><identifier>ISSN: 0804-4643</identifier><identifier>EISSN: 1479-683X</identifier><identifier>DOI: 10.1530/EJE-11-0918</identifier><identifier>PMID: 22189997</identifier><language>eng</language><publisher>Bristol: BioScientifica</publisher><subject>Adrenal Cortex Neoplasms - drug therapy ; Adrenal Cortex Neoplasms - pathology ; Adrenals. Adrenal axis. Renin-angiotensin system (diseases) ; Adrenocortical Carcinoma - drug therapy ; Adrenocortical Carcinoma - pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Benzenesulfonates - administration & dosage ; Biological and medical sciences ; Cell Line, Tumor ; Clinical Study ; Disease-Free Survival ; Drug Administration Schedule ; Endocrinopathies ; Female ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Humans ; Male ; Malignant tumors ; Medical sciences ; Middle Aged ; Niacinamide - analogs & derivatives ; Paclitaxel - administration & dosage ; Phenylurea Compounds ; Prospective Studies ; Pyridines - administration & dosage ; Vertebrates: endocrinology</subject><ispartof>European journal of endocrinology, 2012-03, Vol.166 (3), p.451-458</ispartof><rights>2012 European Society of Endocrinology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b439t-8716f7c7019571b651835ae9d89f0e229e4a0438deff78483405b7fced1f730b3</citedby><cites>FETCH-LOGICAL-b439t-8716f7c7019571b651835ae9d89f0e229e4a0438deff78483405b7fced1f730b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,783,787,27936,27937</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25698343$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22189997$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Berruti, Alfredo</creatorcontrib><creatorcontrib>Sperone, Paola</creatorcontrib><creatorcontrib>Ferrero, Anna</creatorcontrib><creatorcontrib>Germano, Antonina</creatorcontrib><creatorcontrib>Ardito, Arianna</creatorcontrib><creatorcontrib>Priola, Adriano Massimiliano</creatorcontrib><creatorcontrib>De Francia, Silvia</creatorcontrib><creatorcontrib>Volante, Marco</creatorcontrib><creatorcontrib>Daffara, Fulvia</creatorcontrib><creatorcontrib>Generali, Daniele</creatorcontrib><creatorcontrib>Leboulleux, Sophie</creatorcontrib><creatorcontrib>Perotti, Paola</creatorcontrib><creatorcontrib>Baudin, Eric</creatorcontrib><creatorcontrib>Papotti, Mauro</creatorcontrib><creatorcontrib>Terzolo, Massimo</creatorcontrib><title>Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma</title><title>European journal of endocrinology</title><addtitle>Eur J Endocrinol</addtitle><description>BackgroundThere is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.ObjectiveWe assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.DesignMulticenter, prospective phase II trial.SettingReferral centers for ACC.MethodsTwenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m2 every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.ResultsTumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose–response and time–response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.ConclusionsDespite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.</description><subject>Adrenal Cortex Neoplasms - drug therapy</subject><subject>Adrenal Cortex Neoplasms - pathology</subject><subject>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</subject><subject>Adrenocortical Carcinoma - drug therapy</subject><subject>Adrenocortical Carcinoma - pathology</subject><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Benzenesulfonates - administration & dosage</subject><subject>Biological and medical sciences</subject><subject>Cell Line, Tumor</subject><subject>Clinical Study</subject><subject>Disease-Free Survival</subject><subject>Drug Administration Schedule</subject><subject>Endocrinopathies</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Male</subject><subject>Malignant tumors</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Niacinamide - analogs & derivatives</subject><subject>Paclitaxel - administration & dosage</subject><subject>Phenylurea Compounds</subject><subject>Prospective Studies</subject><subject>Pyridines - administration & dosage</subject><subject>Vertebrates: endocrinology</subject><issn>0804-4643</issn><issn>1479-683X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp90L9vEzEUwHELgWgoTOzICxM66hf7zvaIqhSCKsEAEtvpnf2sGC6-yHbV5r_HUQpsTPbwef7xZew1iPfQS3G1-bzpADphwTxhK1DadoORP56ylTBCdWpQ8oK9KOWnEND24jm7WK_BWGv1ij183WEhvt3yUu_8kS-B3xP9mo_8gG6OFR9o5pg8L0vGQClOHAsv5Jbkr-ouZt_NMRGvO8p4OPKY2mCNlGrh97HuOPpMaXFLrtHhzB1mF9Oyx5fsWcC50KvH9ZJ9v9l8u_7U3X75uL3-cNtNStraGQ1D0E4LsL2GaejByB7JemODoPXakkKhpPEUgjbKSCX6SQdHHoKWYpKX7N35XJeXUjKF8ZDjHvNxBDGe-o2t3wgwnvo1_easD3fTnvxf-ydYA28fAZb2n5AxuVj-uX6w7Q2yOTi7KS7FnXrE0AL89_LflJiJsw</recordid><startdate>20120301</startdate><enddate>20120301</enddate><creator>Berruti, Alfredo</creator><creator>Sperone, Paola</creator><creator>Ferrero, Anna</creator><creator>Germano, Antonina</creator><creator>Ardito, Arianna</creator><creator>Priola, Adriano Massimiliano</creator><creator>De Francia, Silvia</creator><creator>Volante, Marco</creator><creator>Daffara, Fulvia</creator><creator>Generali, Daniele</creator><creator>Leboulleux, Sophie</creator><creator>Perotti, Paola</creator><creator>Baudin, Eric</creator><creator>Papotti, Mauro</creator><creator>Terzolo, Massimo</creator><general>BioScientifica</general><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></search><sort><creationdate>20120301</creationdate><title>Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma</title><author>Berruti, Alfredo ; Sperone, Paola ; Ferrero, Anna ; Germano, Antonina ; Ardito, Arianna ; Priola, Adriano Massimiliano ; De Francia, Silvia ; Volante, Marco ; Daffara, Fulvia ; Generali, Daniele ; Leboulleux, Sophie ; Perotti, Paola ; Baudin, Eric ; Papotti, Mauro ; Terzolo, Massimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b439t-8716f7c7019571b651835ae9d89f0e229e4a0438deff78483405b7fced1f730b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adrenal Cortex Neoplasms - drug therapy</topic><topic>Adrenal Cortex Neoplasms - pathology</topic><topic>Adrenals. Adrenal axis. Renin-angiotensin system (diseases)</topic><topic>Adrenocortical Carcinoma - drug therapy</topic><topic>Adrenocortical Carcinoma - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Benzenesulfonates - administration & dosage</topic><topic>Biological and medical sciences</topic><topic>Cell Line, Tumor</topic><topic>Clinical Study</topic><topic>Disease-Free Survival</topic><topic>Drug Administration Schedule</topic><topic>Endocrinopathies</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Male</topic><topic>Malignant tumors</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Niacinamide - analogs & derivatives</topic><topic>Paclitaxel - administration & dosage</topic><topic>Phenylurea Compounds</topic><topic>Prospective Studies</topic><topic>Pyridines - administration & dosage</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Berruti, Alfredo</creatorcontrib><creatorcontrib>Sperone, Paola</creatorcontrib><creatorcontrib>Ferrero, Anna</creatorcontrib><creatorcontrib>Germano, Antonina</creatorcontrib><creatorcontrib>Ardito, Arianna</creatorcontrib><creatorcontrib>Priola, Adriano Massimiliano</creatorcontrib><creatorcontrib>De Francia, Silvia</creatorcontrib><creatorcontrib>Volante, Marco</creatorcontrib><creatorcontrib>Daffara, Fulvia</creatorcontrib><creatorcontrib>Generali, Daniele</creatorcontrib><creatorcontrib>Leboulleux, Sophie</creatorcontrib><creatorcontrib>Perotti, Paola</creatorcontrib><creatorcontrib>Baudin, Eric</creatorcontrib><creatorcontrib>Papotti, Mauro</creatorcontrib><creatorcontrib>Terzolo, Massimo</creatorcontrib><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><jtitle>European journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Berruti, Alfredo</au><au>Sperone, Paola</au><au>Ferrero, Anna</au><au>Germano, Antonina</au><au>Ardito, Arianna</au><au>Priola, Adriano Massimiliano</au><au>De Francia, Silvia</au><au>Volante, Marco</au><au>Daffara, Fulvia</au><au>Generali, Daniele</au><au>Leboulleux, Sophie</au><au>Perotti, Paola</au><au>Baudin, Eric</au><au>Papotti, Mauro</au><au>Terzolo, Massimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma</atitle><jtitle>European journal of endocrinology</jtitle><addtitle>Eur J Endocrinol</addtitle><date>2012-03-01</date><risdate>2012</risdate><volume>166</volume><issue>3</issue><spage>451</spage><epage>458</epage><pages>451-458</pages><issn>0804-4643</issn><eissn>1479-683X</eissn><abstract>BackgroundThere is a strong rationale in the use of antiangiogenic therapy in the management of adrenocortical carcinoma (ACC). Metronomic administration of chemotherapy and antiangiogenic drugs can be synergistic in targeting endothelial cells.ObjectiveWe assessed the activity of sorafenib plus metronomic paclitaxel as second/third-line therapy in advanced ACC patients. We also tested the activity of sorafenib and paclitaxel against NCI-H295R in vitro.DesignMulticenter, prospective phase II trial.SettingReferral centers for ACC.MethodsTwenty-five consecutive metastatic ACC patients who progressed after mitotane plus one or two chemotherapy lines were planned to be enrolled. The patients received a combination of i.v. paclitaxel (60 mg/m2 every week) and oral sorafenib (400 mg twice a day) till progression. The primary aim was to measure the progression-free survival rate after 4 months and the secondary aims were to assess the objective response rate and toxicity.ResultsTumor progression was observed in nine evaluable patients at the first assessment. These results led to the premature interruption of the trial. The treatment was well tolerated. The most relevant toxicities were fatigue, being grade 2 or 3 in four patients, and hypophosphatemia, being grade 3 in three patients. In the in vitro study, sorafenib impaired the viability of H295R cells with dose–response and time–response relationships. The in vitro sorafenib activity was not increased in combination with paclitaxel.ConclusionsDespite the in vitro activity, sorafenib plus weekly paclitaxel is an inactive salvage treatment in patients with advanced ACC and should not be recommended.</abstract><cop>Bristol</cop><pub>BioScientifica</pub><pmid>22189997</pmid><doi>10.1530/EJE-11-0918</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | European journal of endocrinology, 2012-03, Vol.166 (3), p.451-458 |
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| subjects | Adrenal Cortex Neoplasms - drug therapy Adrenal Cortex Neoplasms - pathology Adrenals. Adrenal axis. Renin-angiotensin system (diseases) Adrenocortical Carcinoma - drug therapy Adrenocortical Carcinoma - pathology Adult Aged Antineoplastic Combined Chemotherapy Protocols - administration & dosage Benzenesulfonates - administration & dosage Biological and medical sciences Cell Line, Tumor Clinical Study Disease-Free Survival Drug Administration Schedule Endocrinopathies Female Follow-Up Studies Fundamental and applied biological sciences. Psychology Humans Male Malignant tumors Medical sciences Middle Aged Niacinamide - analogs & derivatives Paclitaxel - administration & dosage Phenylurea Compounds Prospective Studies Pyridines - administration & dosage Vertebrates: endocrinology |
| title | Phase II study of weekly paclitaxel and sorafenib as second/third-line therapy in patients with adrenocortical carcinoma |
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