Circulating Endothelial Progenitor Cells in Castration Resistant Prostate Cancer: A Randomized, Controlled, Biomarker Study
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{"title"=>"Circulating endothelial progenitor cells in castration resistant prostate cancer: A randomized, controlled, biomarker study", "type"=>"journal", "authors"=>[{"first_name"=>"Thorsten", "last_name"=>"Fuereder", "scopus_author_id"=>"16063535400"}, {"first_name"=>"Volker", "last_name"=>"Wacheck", "scopus_author_id"=>"6701686790"}, {"first_name"=>"Sabine", "last_name"=>"Strommer", "scopus_author_id"=>"6506558326"}, {"first_name"=>"Peter", "last_name"=>"Horak", "scopus_author_id"=>"10243987000"}, {"first_name"=>"Marion", "last_name"=>"Gerschpacher", "scopus_author_id"=>"6507282894"}, {"first_name"=>"Wolfgang", "last_name"=>"Lamm", "scopus_author_id"=>"9634195500"}, {"first_name"=>"Danijel", "last_name"=>"Kivaranovic", "scopus_author_id"=>"56145538100"}, {"first_name"=>"Michael", "last_name"=>"Krainer", "scopus_author_id"=>"57194107240"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84899683171", "doi"=>"10.1371/journal.pone.0095310", "issn"=>"19326203", "pui"=>"372991440", "pmid"=>"24755958", "scopus"=>"2-s2.0-84899683171"}, "id"=>"0701a72a-8de6-3489-b913-c5ab2f716cef", "abstract"=>"BACKGROUND: Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.\\n\\nPATIENTS AND METHODS: Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.\\n\\nRESULTS: A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6-3.6 months, 95% CI) and 6.2 months (4.9-7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.\\n\\nCONCLUSION: In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.\\n\\nTRIAL REGISTERY: clinicaltrialsregister.eu EudraCT 2007-003705-27.", "link"=>"http://www.mendeley.com/research/circulating-endothelial-progenitor-cells-castration-resistant-prostate-cancer-randomized-controlled", "reader_count"=>16, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Researcher"=>2, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Researcher"=>2, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>9, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1552671"], "description"=>"<p>Representative example of flow cytometry dot plots chosen for CEP measurements. The left panel shows CD146 positive endothelial cells of which a small number were CD133 positive accounting for CEPs as indicated by the red arrow (right panel) (a). Regression analysis employing a linear mixed model of total CEC (b), viable CEC (c) and CEP (d) counts on a logarithmic scale of docetaxel (blue) and docetaxel/sunitinib treated patients. Each dot represents a single patient. X-axis represents cycles and time points; Y-axis represents CEP and CEC numbers on a logarithmic scale.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases", "cec"], "article_id"=>1072731, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CEP_and_CEC_kinetics_/1072731", "title"=>"CEP and CEC kinetics.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552679"], "description"=>"<p>Bone scan results.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases"], "article_id"=>1072739, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.t002", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bone_scan_results_/1072739", "title"=>"Bone scan results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552661"], "description"=>"<p>Consort flow diagram.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases"], "article_id"=>1072721, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.g001", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Consort_flow_diagram_/1072721", "title"=>"Consort flow diagram.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552678"], "description"=>"<p>Kaplan-Meier curves depicting progression free survival between sunitinib/docetaxel arm (orange) and docetaxel monotherapy arm (blue). Black bars represent censored patients.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases"], "article_id"=>1072738, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.g004", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PFS_between_both_treatment_arms_/1072738", "title"=>"PFS between both treatment arms.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552681"], "description"=>"<p>Patient characteristics.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases"], "article_id"=>1072741, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.t001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_/1072741", "title"=>"Patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552698", "https://ndownloader.figshare.com/files/1552699", "https://ndownloader.figshare.com/files/1552700", "https://ndownloader.figshare.com/files/1552701"], "description"=>"<div><p>Background</p><p>Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients.</p><p>Patients and methods</p><p>Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m<sup>2</sup>) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy.</p><p>Results</p><p>A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable.</p><p>Conclusion</p><p>In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS.</p><p>Trial Registery</p><p>clinicaltrialsregister.eu <a href=\"https://www.clinicaltrialsregister.eu/ctr-search/search?query=2007-003705-27\" target=\"_blank\">EudraCT 2007-003705-27</a></p></div>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases", "endothelial", "progenitor", "cells", "castration", "resistant", "prostate", "biomarker"], "article_id"=>1072758, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0095310.s001", "https://dx.doi.org/10.1371/journal.pone.0095310.s002", "https://dx.doi.org/10.1371/journal.pone.0095310.s003", "https://dx.doi.org/10.1371/journal.pone.0095310.s004"], "stats"=>{"downloads"=>17, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Circulating_Endothelial_Progenitor_Cells_in_Castration_Resistant_Prostate_Cancer_A_Randomized_Controlled_Biomarker_Study_/1072758", "title"=>"Circulating Endothelial Progenitor Cells in Castration Resistant Prostate Cancer: A Randomized, Controlled, Biomarker Study", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552680"], "description"=>"<p>Part II patient characteristics.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases", "ii"], "article_id"=>1072740, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.t003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Part_II_patient_characteristics_/1072740", "title"=>"Part II patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-04-22 09:55:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/1552675"], "description"=>"<p>Waterfall plot of PSA response to docetaxel (blue) and sunitinib/docetaxel (yellow) in CRPC patients.</p>", "links"=>[], "tags"=>["oncology", "Cancers and neoplasms", "Genitourinary tract tumors", "Prostate cancer", "Cancer treatment", "Antiangiogenesis therapy", "Clinical trials (cancer treatment)", "urology", "Prostate diseases"], "article_id"=>1072735, "categories"=>["Biological Sciences"], "users"=>["Thorsten Fuereder", "Volker Wacheck", "Sabine Strommer", "Peter Horak", "Marion Gerschpacher", "Wolfgang Lamm", "Danijel Kivaranovic", "Michael Krainer"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0095310.g003", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PSA_response_/1072735", "title"=>"PSA response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-22 09:55:33"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences/Pharmaceutics", "average_usage"=>[299, 467]}, {"subject_area"=>"/Medicine and health sciences/Urology", "average_usage"=>[287, 446]}]}
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