Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805
Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure. We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration. Patients and Method...
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| Veröffentlicht in: | Clinical cancer research 2005-06, Vol.11 (11), p.4176-4181 |
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| creator | Byrd, John C Peterson, Bercedis L Gabrilove, Janice Odenike, Olatoyosi M Grever, Michael R Rai, Kanti Larson, Richard A |
| description | Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure.
We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration.
Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial
received flavopiridol (50 mg/m 2 /d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m 2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort)
cycles of therapy.
Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9
(60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had
progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%)
having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive
disease. The progression-free survival for responders in the IVB trial was 3, 3, 9, and 19 months. The median progression-free
survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4)
for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31)
for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue.
Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing
alternative schedules of administration. |
| doi_str_mv | 10.1158/1078-0432.CCR-04-2276 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_19725937</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>19725937</sourcerecordid><originalsourceid>FETCH-LOGICAL-c372t-1731ba71d50588fd43ed5025da0f542f4d38be5b45172cbefdb85bfdd9e236ea3</originalsourceid><addsrcrecordid>eNpVkdtq3DAQhkVpaU59hBZdFXLhVAdr5e1dY5oDLBSS9FrI1qhWa1uuZCX4rfqIkbtbQkGgH-af-Zn5EHpPyQWlovpEiawKUnJ2Udd3WRSMyc0rdEyFkAVnG_E663-eI3QS409CaElJ-RYdUbHlhIvyGP15CKDnAcYZe4vvoNdTBIPrLvjRtXi3DFPn22VeNaRfMDiNmwVLVtz4FHDtx9mNyaeIb0ebovMj9gHTffXS9_8VLL7q9aOfXHDG959zXEz9HLENfsC1HlsIWI_mJek6-DThS3w_J7Nguq2IOENvrO4jvDv8p-j71deH-qbYfbu-rb_sipZLNhdUctpoSY0goqqsKTlkyYTRxIqS2dLwqgHRlIJK1jZgTVOJxhqzBcY3oPkp-rifOwX_O0Gc1eBiC32vR8jrKrqVLF9RZqPYG9vgYwxg1RTcoMOiKFErKrViUCsGlVFloVZUue_DISA1A5iXrgObbDjfGzr3o3tyAVT790QBIujQdnn4-kqahz0DOgKfhQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>19725937</pqid></control><display><type>article</type><title>Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Byrd, John C ; Peterson, Bercedis L ; Gabrilove, Janice ; Odenike, Olatoyosi M ; Grever, Michael R ; Rai, Kanti ; Larson, Richard A</creator><creatorcontrib>Byrd, John C ; Peterson, Bercedis L ; Gabrilove, Janice ; Odenike, Olatoyosi M ; Grever, Michael R ; Rai, Kanti ; Larson, Richard A ; Cancer and Leukemia Group B ; the Cancer and Leukemia Group B</creatorcontrib><description>Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure.
We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration.
Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial
received flavopiridol (50 mg/m 2 /d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m 2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort)
cycles of therapy.
Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9
(60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had
progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%)
having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive
disease. The progression-free survival for responders in the IVB trial was 3, 3, 9, and 19 months. The median progression-free
survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4)
for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31)
for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue.
Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing
alternative schedules of administration.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>DOI: 10.1158/1078-0432.CCR-04-2276</identifier><identifier>PMID: 15930354</identifier><language>eng</language><publisher>United States: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - administration & dosage ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; CDKs and CDK inhibitors ; Drug Administration Schedule ; Female ; Flavonoids - administration & dosage ; Flavonoids - adverse effects ; Flavonoids - therapeutic use ; Hematologic, other ; Humans ; Infusion Pumps ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - pathology ; Leukemias and lymphonas ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neutropenia - chemically induced ; Piperidines - administration & dosage ; Piperidines - adverse effects ; Piperidines - therapeutic use ; Survival Analysis ; Thrombocytopenia - chemically induced ; Treatment Outcome</subject><ispartof>Clinical cancer research, 2005-06, Vol.11 (11), p.4176-4181</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c372t-1731ba71d50588fd43ed5025da0f542f4d38be5b45172cbefdb85bfdd9e236ea3</citedby><cites>FETCH-LOGICAL-c372t-1731ba71d50588fd43ed5025da0f542f4d38be5b45172cbefdb85bfdd9e236ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3354,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15930354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Byrd, John C</creatorcontrib><creatorcontrib>Peterson, Bercedis L</creatorcontrib><creatorcontrib>Gabrilove, Janice</creatorcontrib><creatorcontrib>Odenike, Olatoyosi M</creatorcontrib><creatorcontrib>Grever, Michael R</creatorcontrib><creatorcontrib>Rai, Kanti</creatorcontrib><creatorcontrib>Larson, Richard A</creatorcontrib><creatorcontrib>Cancer and Leukemia Group B</creatorcontrib><creatorcontrib>the Cancer and Leukemia Group B</creatorcontrib><title>Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure.
We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration.
Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial
received flavopiridol (50 mg/m 2 /d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m 2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort)
cycles of therapy.
Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9
(60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had
progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%)
having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive
disease. The progression-free survival for responders in the IVB trial was 3, 3, 9, and 19 months. The median progression-free
survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4)
for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31)
for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue.
Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing
alternative schedules of administration.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - administration & dosage</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>CDKs and CDK inhibitors</subject><subject>Drug Administration Schedule</subject><subject>Female</subject><subject>Flavonoids - administration & dosage</subject><subject>Flavonoids - adverse effects</subject><subject>Flavonoids - therapeutic use</subject><subject>Hematologic, other</subject><subject>Humans</subject><subject>Infusion Pumps</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</subject><subject>Leukemias and lymphonas</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local</subject><subject>Neoplasm Staging</subject><subject>Neutropenia - chemically induced</subject><subject>Piperidines - administration & dosage</subject><subject>Piperidines - adverse effects</subject><subject>Piperidines - therapeutic use</subject><subject>Survival Analysis</subject><subject>Thrombocytopenia - chemically induced</subject><subject>Treatment Outcome</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkdtq3DAQhkVpaU59hBZdFXLhVAdr5e1dY5oDLBSS9FrI1qhWa1uuZCX4rfqIkbtbQkGgH-af-Zn5EHpPyQWlovpEiawKUnJ2Udd3WRSMyc0rdEyFkAVnG_E663-eI3QS409CaElJ-RYdUbHlhIvyGP15CKDnAcYZe4vvoNdTBIPrLvjRtXi3DFPn22VeNaRfMDiNmwVLVtz4FHDtx9mNyaeIb0ebovMj9gHTffXS9_8VLL7q9aOfXHDG959zXEz9HLENfsC1HlsIWI_mJek6-DThS3w_J7Nguq2IOENvrO4jvDv8p-j71deH-qbYfbu-rb_sipZLNhdUctpoSY0goqqsKTlkyYTRxIqS2dLwqgHRlIJK1jZgTVOJxhqzBcY3oPkp-rifOwX_O0Gc1eBiC32vR8jrKrqVLF9RZqPYG9vgYwxg1RTcoMOiKFErKrViUCsGlVFloVZUue_DISA1A5iXrgObbDjfGzr3o3tyAVT790QBIujQdnn4-kqahz0DOgKfhQ</recordid><startdate>20050601</startdate><enddate>20050601</enddate><creator>Byrd, John C</creator><creator>Peterson, Bercedis L</creator><creator>Gabrilove, Janice</creator><creator>Odenike, Olatoyosi M</creator><creator>Grever, Michael R</creator><creator>Rai, Kanti</creator><creator>Larson, Richard A</creator><general>American Association for Cancer Research</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>7T5</scope><scope>H94</scope></search><sort><creationdate>20050601</creationdate><title>Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805</title><author>Byrd, John C ; Peterson, Bercedis L ; Gabrilove, Janice ; Odenike, Olatoyosi M ; Grever, Michael R ; Rai, Kanti ; Larson, Richard A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c372t-1731ba71d50588fd43ed5025da0f542f4d38be5b45172cbefdb85bfdd9e236ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Agents - administration & dosage</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>CDKs and CDK inhibitors</topic><topic>Drug Administration Schedule</topic><topic>Female</topic><topic>Flavonoids - administration & dosage</topic><topic>Flavonoids - adverse effects</topic><topic>Flavonoids - therapeutic use</topic><topic>Hematologic, other</topic><topic>Humans</topic><topic>Infusion Pumps</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</topic><topic>Leukemia, Lymphocytic, Chronic, B-Cell - pathology</topic><topic>Leukemias and lymphonas</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Recurrence, Local</topic><topic>Neoplasm Staging</topic><topic>Neutropenia - chemically induced</topic><topic>Piperidines - administration & dosage</topic><topic>Piperidines - adverse effects</topic><topic>Piperidines - therapeutic use</topic><topic>Survival Analysis</topic><topic>Thrombocytopenia - chemically induced</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Byrd, John C</creatorcontrib><creatorcontrib>Peterson, Bercedis L</creatorcontrib><creatorcontrib>Gabrilove, Janice</creatorcontrib><creatorcontrib>Odenike, Olatoyosi M</creatorcontrib><creatorcontrib>Grever, Michael R</creatorcontrib><creatorcontrib>Rai, Kanti</creatorcontrib><creatorcontrib>Larson, Richard A</creatorcontrib><creatorcontrib>Cancer and Leukemia Group B</creatorcontrib><creatorcontrib>the Cancer and Leukemia Group B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Byrd, John C</au><au>Peterson, Bercedis L</au><au>Gabrilove, Janice</au><au>Odenike, Olatoyosi M</au><au>Grever, Michael R</au><au>Rai, Kanti</au><au>Larson, Richard A</au><aucorp>Cancer and Leukemia Group B</aucorp><aucorp>the Cancer and Leukemia Group B</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2005-06-01</date><risdate>2005</risdate><volume>11</volume><issue>11</issue><spage>4176</spage><epage>4181</epage><pages>4176-4181</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>Purpose: Flavopiridol has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine exposure.
We sought to determine if flavopiridol has activity in previously treated CLL using two schedules of administration.
Patients and Methods: Patients with previously treated CLL were enrolled in two sequentially done phase II studies. Patients in the first trial
received flavopiridol (50 mg/m 2 /d) as a continuous infusion (CI) for 72 hours every 2 weeks. Patients in the second trial received flavopiridol 50 mg/m 2 as a 1-hour bolus (IVB) daily for 3 days repeated every 3 weeks. Patients received up to 12 (CI cohort) or 8 (IVB cohort)
cycles of therapy.
Results: Fifteen patients were enrolled in the 72-hour CI phase II trial; 6 (40%) had intermediate-risk (Rai stage I or II) and 9
(60%) had high-risk (Rai stage III and IV) stages. No responses were noted in this group; 27% had stable disease and 73% had
progressive disease. Thirty-six patients were enrolled in the second IVB trial, with 13 (36%) having intermediate and 23 (64%)
having high-risk disease. Four patients (11%) had partial responses, 19 (53%) had stable disease, and 13 (36%) had progressive
disease. The progression-free survival for responders in the IVB trial was 3, 3, 9, and 19 months. The median progression-free
survival was 2 months [95% confidence interval (95% CI), 1.8-3.8] for patients in the CI trial and 3 months (95% CI, 2.5-7.4)
for the IVB trial. The median overall survival was 27 months (95% CI, 20-42) for the CI trial and 24 months (95% CI, 18-31)
for the IVB trial. Toxicity was manageable and included mainly myelosuppression, infections, diarrhea, and fatigue.
Conclusions: Flavopiridol has modest, schedule-dependent clinical activity in relapsed CLL and warrants future investigation utilizing
alternative schedules of administration.</abstract><cop>United States</cop><pub>American Association for Cancer Research</pub><pmid>15930354</pmid><doi>10.1158/1078-0432.CCR-04-2276</doi><tpages>6</tpages></addata></record> |
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| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - administration & dosage Antineoplastic Agents - adverse effects Antineoplastic Agents - therapeutic use CDKs and CDK inhibitors Drug Administration Schedule Female Flavonoids - administration & dosage Flavonoids - adverse effects Flavonoids - therapeutic use Hematologic, other Humans Infusion Pumps Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - pathology Leukemias and lymphonas Male Middle Aged Neoplasm Recurrence, Local Neoplasm Staging Neutropenia - chemically induced Piperidines - administration & dosage Piperidines - adverse effects Piperidines - therapeutic use Survival Analysis Thrombocytopenia - chemically induced Treatment Outcome |
| title | Treatment of Relapsed Chronic Lymphocytic Leukemia by 72-Hour Continuous Infusion or 1-Hour Bolus Infusion of Flavopiridol: Results from Cancer and Leukemia Group B Study 19805 |
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