Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study
Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying...
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| Veröffentlicht in: | Leukemia 2008-04, Vol.22 (4), p.842-849 |
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| creator | San-Miguel, J F Richardson, P G Sonneveld, P Schuster, M W Irwin, D Stadtmauer, E A Facon, T Harousseau, J-L Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D Bladé, J Boccadoro, M Cavenagh, J D Neuwirth, R Boral, A L Esseltine, D-L Anderson, K C |
| description | Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) 80 ml min
−1
). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl ⩽50 ml min
−1
(severe-to-moderate) and >50 ml min
−1
(no/mild impairment). Response rates with bortezomib were similar (36–47%) and time to response rapid (0.7–1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl ⩽50 vs >50 ml min
−1
(
P
=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl ⩽50 vs >50 ml min
−1
. These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment. |
| doi_str_mv | 10.1038/sj.leu.2405087 |
| format | Article |
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−1
). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl ⩽50 ml min
−1
(severe-to-moderate) and >50 ml min
−1
(no/mild impairment). Response rates with bortezomib were similar (36–47%) and time to response rapid (0.7–1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl ⩽50 vs >50 ml min
−1
(
P
=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl ⩽50 vs >50 ml min
−1
. These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/sj.leu.2405087</identifier><identifier>PMID: 18200040</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Aged ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - toxicity ; Apexes ; Biological and medical sciences ; Boronic Acids - administration & dosage ; Boronic Acids - toxicity ; Bortezomib ; Cancer Research ; Complications and side effects ; Creatinine ; Critical Care Medicine ; Dexamethasone ; Dexamethasone - administration & dosage ; Dexamethasone - toxicity ; Diagnosis ; Dosage and administration ; Drug therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Hematologic and hematopoietic diseases ; Hematology ; Humans ; Impairment ; Inhibitor drugs ; Intensive ; Internal Medicine ; Kidney diseases ; Kidneys ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Male ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Middle Aged ; Multiple myeloma ; Multiple Myeloma - complications ; Multiple Myeloma - drug therapy ; Multiple Myeloma - mortality ; Nephrology. Urinary tract diseases ; Nephropathies. Renovascular diseases. Renal failure ; Oncology ; original-article ; Prognosis ; Proteasomes ; Pyrazines - administration & dosage ; Pyrazines - toxicity ; Renal failure ; Renal function ; Renal insufficiency ; Renal Insufficiency - mortality ; Renal Insufficiency - pathology ; Risk factors ; Safety ; Subgroups ; Survival Analysis ; Targeted cancer therapy ; Treatment Outcome</subject><ispartof>Leukemia, 2008-04, Vol.22 (4), p.842-849</ispartof><rights>Springer Nature Limited 2008</rights><rights>2008 INIST-CNRS</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Apr 2008</rights><rights>Nature Publishing Group 2008.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c587t-ec1367e6abf63d56c91044648078f2fac03de0ffc32ff75eaf1ec9b606722e553</citedby><cites>FETCH-LOGICAL-c587t-ec1367e6abf63d56c91044648078f2fac03de0ffc32ff75eaf1ec9b606722e553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/sj.leu.2405087$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/sj.leu.2405087$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20281386$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18200040$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>San-Miguel, J F</creatorcontrib><creatorcontrib>Richardson, P G</creatorcontrib><creatorcontrib>Sonneveld, P</creatorcontrib><creatorcontrib>Schuster, M W</creatorcontrib><creatorcontrib>Irwin, D</creatorcontrib><creatorcontrib>Stadtmauer, E A</creatorcontrib><creatorcontrib>Facon, T</creatorcontrib><creatorcontrib>Harousseau, J-L</creatorcontrib><creatorcontrib>Ben-Yehuda, D</creatorcontrib><creatorcontrib>Lonial, S</creatorcontrib><creatorcontrib>Goldschmidt, H</creatorcontrib><creatorcontrib>Reece, D</creatorcontrib><creatorcontrib>Bladé, J</creatorcontrib><creatorcontrib>Boccadoro, M</creatorcontrib><creatorcontrib>Cavenagh, J D</creatorcontrib><creatorcontrib>Neuwirth, R</creatorcontrib><creatorcontrib>Boral, A L</creatorcontrib><creatorcontrib>Esseltine, D-L</creatorcontrib><creatorcontrib>Anderson, K C</creatorcontrib><title>Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30–50, 51–80 and >80 ml min
−1
). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl ⩽50 ml min
−1
(severe-to-moderate) and >50 ml min
−1
(no/mild impairment). Response rates with bortezomib were similar (36–47%) and time to response rapid (0.7–1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl ⩽50 vs >50 ml min
−1
(
P
=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl ⩽50 vs >50 ml min
−1
. These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.</description><subject>Aged</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Apexes</subject><subject>Biological and medical sciences</subject><subject>Boronic Acids - administration & dosage</subject><subject>Boronic Acids - toxicity</subject><subject>Bortezomib</subject><subject>Cancer Research</subject><subject>Complications and side effects</subject><subject>Creatinine</subject><subject>Critical Care Medicine</subject><subject>Dexamethasone</subject><subject>Dexamethasone - administration & dosage</subject><subject>Dexamethasone - toxicity</subject><subject>Diagnosis</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Drug-Related Side Effects and Adverse Reactions</subject><subject>Female</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Humans</subject><subject>Impairment</subject><subject>Inhibitor drugs</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Kidney diseases</subject><subject>Kidneys</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - complications</subject><subject>Multiple Myeloma - drug therapy</subject><subject>Multiple Myeloma - mortality</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Nephropathies. Renovascular diseases. Renal failure</subject><subject>Oncology</subject><subject>original-article</subject><subject>Prognosis</subject><subject>Proteasomes</subject><subject>Pyrazines - administration & dosage</subject><subject>Pyrazines - toxicity</subject><subject>Renal failure</subject><subject>Renal function</subject><subject>Renal insufficiency</subject><subject>Renal Insufficiency - mortality</subject><subject>Renal Insufficiency - pathology</subject><subject>Risk factors</subject><subject>Safety</subject><subject>Subgroups</subject><subject>Survival Analysis</subject><subject>Targeted cancer therapy</subject><subject>Treatment Outcome</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1ks-L1DAUx4so7uzq1aMExb3NbJLmV70Ny6wKC3pQ8FbS9GWboW1qkiLjX2_KDo7KLjkE3vt8vy8vfIviFcEbgkt1FfebHuYNZZhjJZ8UK8KkWHPOydNihZWSa1FRdlacx7jHeGmK58UZURRjzPCq6HbWOqPNAemxRVFbSAfkLWp8SPDLD65BbkSTTg7GFNFPlzoUYNQ9csOkXRhy-X2uxLnPbRv8gFIHaPtl9x1NnY6AShTT3B5eFM-s7iO8PN4Xxbeb3dfrj-vbzx8-XW9v14YrmdZgSCkkCN1YUbZcmIpgxgRTWCpLrTa4bAFba0pqreSgLQFTNQILSSlwXl4Ul_e-U_A_ZoipHlw00Pd6BD_HmmJRMc5YBt_-B-79HPJmmRGMS1ZSulBvHqUo5kwSKU5Wd7qH2o3Wp6DNMrfeElXJKr-tytTmASqfFgZn_AjW5fo_gsu_BB3oPnXR93NyfowPOpvgYwxg6ym4QYdDTXC9xKSO-zrHpD7GJAteH7eamwHaE37MRQbeHQEdje5t0KNx8Q9HMVWkVMvmV_dczK3xDsLpex4Z_RujP9Kx</recordid><startdate>20080401</startdate><enddate>20080401</enddate><creator>San-Miguel, J F</creator><creator>Richardson, P G</creator><creator>Sonneveld, P</creator><creator>Schuster, M W</creator><creator>Irwin, D</creator><creator>Stadtmauer, E A</creator><creator>Facon, T</creator><creator>Harousseau, J-L</creator><creator>Ben-Yehuda, D</creator><creator>Lonial, S</creator><creator>Goldschmidt, H</creator><creator>Reece, D</creator><creator>Bladé, J</creator><creator>Boccadoro, M</creator><creator>Cavenagh, J D</creator><creator>Neuwirth, R</creator><creator>Boral, A L</creator><creator>Esseltine, D-L</creator><creator>Anderson, K C</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</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><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20080401</creationdate><title>Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study</title><author>San-Miguel, J F ; Richardson, P G ; Sonneveld, P ; Schuster, M W ; Irwin, D ; Stadtmauer, E A ; Facon, T ; Harousseau, J-L ; Ben-Yehuda, D ; Lonial, S ; Goldschmidt, H ; Reece, D ; Bladé, J ; Boccadoro, M ; Cavenagh, J D ; Neuwirth, R ; Boral, A L ; Esseltine, D-L ; Anderson, K C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-ec1367e6abf63d56c91044648078f2fac03de0ffc32ff75eaf1ec9b606722e553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aged</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Apexes</topic><topic>Biological and medical sciences</topic><topic>Boronic Acids - administration & dosage</topic><topic>Boronic Acids - toxicity</topic><topic>Bortezomib</topic><topic>Cancer Research</topic><topic>Complications and side effects</topic><topic>Creatinine</topic><topic>Critical Care Medicine</topic><topic>Dexamethasone</topic><topic>Dexamethasone - administration & dosage</topic><topic>Dexamethasone - toxicity</topic><topic>Diagnosis</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Drug-Related Side Effects and Adverse Reactions</topic><topic>Female</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Humans</topic><topic>Impairment</topic><topic>Inhibitor drugs</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Kidney diseases</topic><topic>Kidneys</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - complications</topic><topic>Multiple Myeloma - drug therapy</topic><topic>Multiple Myeloma - mortality</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Nephropathies. Renovascular diseases. Renal failure</topic><topic>Oncology</topic><topic>original-article</topic><topic>Prognosis</topic><topic>Proteasomes</topic><topic>Pyrazines - administration & dosage</topic><topic>Pyrazines - toxicity</topic><topic>Renal failure</topic><topic>Renal function</topic><topic>Renal insufficiency</topic><topic>Renal Insufficiency - mortality</topic><topic>Renal Insufficiency - pathology</topic><topic>Risk factors</topic><topic>Safety</topic><topic>Subgroups</topic><topic>Survival Analysis</topic><topic>Targeted cancer therapy</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>San-Miguel, J F</creatorcontrib><creatorcontrib>Richardson, P G</creatorcontrib><creatorcontrib>Sonneveld, P</creatorcontrib><creatorcontrib>Schuster, M W</creatorcontrib><creatorcontrib>Irwin, D</creatorcontrib><creatorcontrib>Stadtmauer, E A</creatorcontrib><creatorcontrib>Facon, T</creatorcontrib><creatorcontrib>Harousseau, 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D</au><au>Neuwirth, R</au><au>Boral, A L</au><au>Esseltine, D-L</au><au>Anderson, K C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2008-04-01</date><risdate>2008</risdate><volume>22</volume><issue>4</issue><spage>842</spage><epage>849</epage><pages>842-849</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>Renal impairment is associated with poor prognosis in multiple myeloma (MM). This subgroup analysis of the phase 3 Assessment of Proteasome Inhibition for Extending Remissions (APEX) study of bortezomib vs high-dose dexamethasone assessed efficacy and safety in patients with relapsed MM with varying degrees of renal impairment (creatinine clearance (CrCl) <30, 30–50, 51–80 and >80 ml min
−1
). Time to progression (TTP), overall survival (OS) and safety were compared between subgroups with CrCl ⩽50 ml min
−1
(severe-to-moderate) and >50 ml min
−1
(no/mild impairment). Response rates with bortezomib were similar (36–47%) and time to response rapid (0.7–1.6 months) across subgroups. Although the trend was toward shorter TTP/OS in bortezomib patients with severe-to-moderate vs no/mild impairment, differences were not significant. OS was significantly shorter in dexamethasone patients with CrCl ⩽50 vs >50 ml min
−1
(
P
=0.003), indicating that bortezomib is more effective than dexamethasone in overcoming the detrimental effect of renal impairment. Safety profile of bortezomib was comparable between subgroups. With dexamethasone, grade 3/4 adverse events (AEs), serious AEs and discontinuations for AEs were significantly elevated in patients with CrCl ⩽50 vs >50 ml min
−1
. These results indicate that bortezomib is active and well tolerated in patients with relapsed MM with varying degrees of renal insufficiency. Efficacy/safety were not substantially affected by severe-to-moderate vs no/mild impairment.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18200040</pmid><doi>10.1038/sj.leu.2405087</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2008-04, Vol.22 (4), p.842-849 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_20694544 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Aged Antineoplastic Agents - administration & dosage Antineoplastic Agents - toxicity Apexes Biological and medical sciences Boronic Acids - administration & dosage Boronic Acids - toxicity Bortezomib Cancer Research Complications and side effects Creatinine Critical Care Medicine Dexamethasone Dexamethasone - administration & dosage Dexamethasone - toxicity Diagnosis Dosage and administration Drug therapy Drug-Related Side Effects and Adverse Reactions Female Hematologic and hematopoietic diseases Hematology Humans Impairment Inhibitor drugs Intensive Internal Medicine Kidney diseases Kidneys Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Male Medical prognosis Medical sciences Medicine Medicine & Public Health Middle Aged Multiple myeloma Multiple Myeloma - complications Multiple Myeloma - drug therapy Multiple Myeloma - mortality Nephrology. Urinary tract diseases Nephropathies. Renovascular diseases. Renal failure Oncology original-article Prognosis Proteasomes Pyrazines - administration & dosage Pyrazines - toxicity Renal failure Renal function Renal insufficiency Renal Insufficiency - mortality Renal Insufficiency - pathology Risk factors Safety Subgroups Survival Analysis Targeted cancer therapy Treatment Outcome |
| title | Efficacy and safety of bortezomib in patients with renal impairment: results from the APEX phase 3 study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T22%3A57%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Efficacy%20and%20safety%20of%20bortezomib%20in%20patients%20with%20renal%20impairment:%20results%20from%20the%20APEX%20phase%203%20study&rft.jtitle=Leukemia&rft.au=San-Miguel,%20J%20F&rft.date=2008-04-01&rft.volume=22&rft.issue=4&rft.spage=842&rft.epage=849&rft.pages=842-849&rft.issn=0887-6924&rft.eissn=1476-5551&rft.coden=LEUKED&rft_id=info:doi/10.1038/sj.leu.2405087&rft_dat=%3Cgale_proqu%3EA189797229%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=220547176&rft_id=info:pmid/18200040&rft_galeid=A189797229&rfr_iscdi=true |