Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel.
Identifieur interne : 000311 ( Main/Exploration ); précédent : 000310; suivant : 000312Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel.
Auteurs : Charles J. Ryan [États-Unis] ; Sandipan Dutta [États-Unis] ; William K. Kelly [États-Unis] ; Rob Middleberg [États-Unis] ; Carly Russell [États-Unis] ; Michael J. Morris [États-Unis] ; Mary-Ellen Taplin [États-Unis] ; Susan Halabi [États-Unis]Source :
- Clinical genitourinary cancer [ 1938-0682 ] ; 2020.
Abstract
BACKGROUND
Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.
MATERIALS AND METHODS
Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.
RESULTS
Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).
CONCLUSION
Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.
DOI: 10.1016/j.clgc.2019.10.002
PubMed: 32273234
PubMed Central: PMC7252587
Affiliations:
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Electronic address: ryanc@umn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis</wicri:cityArea></affiliation></author><author><name sortKey="Dutta, Sandipan" sort="Dutta, Sandipan" uniqKey="Dutta S" first="Sandipan" last="Dutta">Sandipan Dutta</name><affiliation wicri:level="2"><nlm:affiliation>Duke University Medical Center, Durham, NC.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Kelly, William K" sort="Kelly, William K" uniqKey="Kelly W" first="William K" last="Kelly">William K. 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Ryan</name><affiliation wicri:level="2"><nlm:affiliation>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis, MN. Electronic address: ryanc@umn.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis</wicri:cityArea></affiliation></author><author><name sortKey="Dutta, Sandipan" sort="Dutta, Sandipan" uniqKey="Dutta S" first="Sandipan" last="Dutta">Sandipan Dutta</name><affiliation wicri:level="2"><nlm:affiliation>Duke University Medical Center, Durham, NC.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Duke University Medical Center, Durham</wicri:cityArea></affiliation></author><author><name sortKey="Kelly, William K" sort="Kelly, William K" uniqKey="Kelly W" first="William K" last="Kelly">William K. Kelly</name><affiliation wicri:level="2"><nlm:affiliation>Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia</wicri:cityArea></affiliation></author><author><name sortKey="Middleberg, Rob" sort="Middleberg, Rob" uniqKey="Middleberg R" first="Rob" last="Middleberg">Rob Middleberg</name><affiliation wicri:level="2"><nlm:affiliation>NMS Labs, Willow Grove, PA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Pennsylvanie</region></placeName><wicri:cityArea>NMS Labs, Willow Grove</wicri:cityArea></affiliation></author><author><name sortKey="Russell, Carly" sort="Russell, Carly" uniqKey="Russell C" first="Carly" last="Russell">Carly Russell</name><affiliation wicri:level="2"><nlm:affiliation>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis, MN.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis</wicri:cityArea></affiliation></author><author><name sortKey="Morris, Michael J" sort="Morris, Michael J" uniqKey="Morris M" first="Michael J" last="Morris">Michael J. Morris</name><affiliation wicri:level="2"><nlm:affiliation>Memorial Sloan Kettering Cancer, New York, NY.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Memorial Sloan Kettering Cancer, New York</wicri:cityArea></affiliation></author><author><name sortKey="Taplin, Mary Ellen" sort="Taplin, Mary Ellen" uniqKey="Taplin M" first="Mary-Ellen" last="Taplin">Mary-Ellen Taplin</name><affiliation wicri:level="2"><nlm:affiliation>Dana-Farber/Partners Cancer Care, Harvard Medical School, Boston, MA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Dana-Farber/Partners Cancer Care, Harvard Medical School, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Halabi, Susan" sort="Halabi, Susan" uniqKey="Halabi S" first="Susan" last="Halabi">Susan Halabi</name><affiliation wicri:level="2"><nlm:affiliation>Duke University Medical Center, Durham, NC.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Duke University Medical Center, Durham</wicri:cityArea></affiliation></author></analytic><series><title level="j">Clinical genitourinary cancer</title><idno type="eISSN">1938-0682</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>BACKGROUND</b></p><p>Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.</p></div><div type="abstract" xml:lang="en"><p><b>MATERIALS AND METHODS</b></p><p>Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.</p></div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">32273234</PMID><DateRevised><Year>2020</Year><Month>10</Month><Day>02</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1938-0682</ISSN><JournalIssue CitedMedium="Internet"><Volume>18</Volume><Issue>3</Issue><PubDate><Year>2020</Year><Month>06</Month></PubDate></JournalIssue><Title>Clinical genitourinary cancer</Title><ISOAbbreviation>Clin Genitourin Cancer</ISOAbbreviation></Journal><ArticleTitle>Androgens and Overall Survival in Patients With Metastatic Castration-resistant Prostate Cancer Treated With Docetaxel.</ArticleTitle><Pagination><MedlinePgn>222-229.e2</MedlinePgn></Pagination><ELocationID EIdType="pii" ValidYN="Y">S1558-7673(19)30306-4</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.clgc.2019.10.002</ELocationID><Abstract><AbstractText Label="BACKGROUND">Pre-treatment androgen levels are associated with overall survival (OS) in patients with metastatic castration-resistant prostate cancer (CRPC) treated with androgen synthesis inhibitors. The current study sought to determine whether pre-treatment serum androgens predict clinical outcome among patients with metastatic CRPC treated with docetaxel chemotherapy.</AbstractText><AbstractText Label="MATERIALS AND METHODS">Data were obtained from 1050 men who were chemotherapy-naive prior to treatment with docetaxel, prednisone, and either bevacizumab or placebo (CALGB 90401). Pretreatment serum assays for testosterone, androstenedione, and dehydroepiandrosterone (DHEA) were performed with tandem liquid chromatography-mass spectrometry.</AbstractText><AbstractText Label="RESULTS">Median values for testosterone, androstenedione, and DHEA were 1.00, 13.50, and 8.12 ng/dL, respectively. The median was used to define the midpoint between low and high values. In univariate analysis, median OS for low versus high levels was 21.4 and 24.2 months for testosterone, 23.8 and 21.9 months for androstenedione, and 20.2 and 25.2 months for DHEA (P = NS). In multivariable analysis of all androgens, baseline DHEA was prognostic of ≥ 50% PSA decline from baseline (P = .008). In multivariable analysis adjusting for 10 known prognostic values and prior ketoconazole use for metastatic CRPC, a 10-unit increase in baseline testosterone increased risk of death (hazard ratio, 1.11; 95% confidence interval, 1.01-1.23; P = .039), whereas a 10-unit increase in androstenedione lowered risk of death (hazard ratio, 0.92; 95% confidence interval, 0.88-0.97; P = .001).</AbstractText><AbstractText Label="CONCLUSION">Consistent with prior studies, higher androstenedione levels in patients with metastatic CRPC treated with docetaxel are associated with improved survival. However pretreatment levels of other androgen levels are associated with varied effects on clinical outcome in chemotherapy-treated patients.</AbstractText><CopyrightInformation>Copyright © 2019 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ryan</LastName><ForeName>Charles J</ForeName><Initials>CJ</Initials><AffiliationInfo><Affiliation>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis, MN. Electronic address: ryanc@umn.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dutta</LastName><ForeName>Sandipan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Duke University Medical Center, Durham, NC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kelly</LastName><ForeName>William K</ForeName><Initials>WK</Initials><AffiliationInfo><Affiliation>Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Middleberg</LastName><ForeName>Rob</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>NMS Labs, Willow Grove, PA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Russell</LastName><ForeName>Carly</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Division of Hematology, Oncology and Transplantation University of Minnesota, Masonic Cancer Center, Minneapolis, MN.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morris</LastName><ForeName>Michael J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Memorial Sloan Kettering Cancer, New York, NY.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Taplin</LastName><ForeName>Mary-Ellen</ForeName><Initials>ME</Initials><AffiliationInfo><Affiliation>Dana-Farber/Partners Cancer Care, Harvard Medical School, Boston, MA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Halabi</LastName><ForeName>Susan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Duke University Medical Center, Durham, NC.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><CollectiveName>Alliance for Clinical Trials in Oncology Genitourinary Committee</CollectiveName></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>U10 CA180821</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 CA008748</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R21 CA195424</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U10 CA180882</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>U24 CA196171</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013486">Research Support, U.S. Gov't, Non-P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2019</Year><Month>10</Month><Day>17</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Clin Genitourin Cancer</MedlineTA><NlmUniqueID>101260955</NlmUniqueID><ISSNLinking>1558-7673</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">Castration resistant prostate cancer</Keyword><Keyword MajorTopicYN="Y">DHEA</Keyword><Keyword MajorTopicYN="Y">Prognostic biomarker</Keyword><Keyword MajorTopicYN="Y">Serum androgens</Keyword><Keyword MajorTopicYN="Y">Testosterone</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>01</Month><Day>15</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2019</Year><Month>10</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2019</Year><Month>10</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="pmc-release"><Year>2021</Year><Month>06</Month><Day>01</Day></PubMedPubDate><PubMedPubDate 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IdType="pubmed">17404083</ArticleId></ArticleIdList></Reference></ReferenceList></PubmedData></pubmed><affiliations><list><country><li>États-Unis</li></country><region><li>Caroline du Nord</li><li>Massachusetts</li><li>Minnesota</li><li>Pennsylvanie</li><li>État de New York</li></region></list><tree><country name="États-Unis"><region name="Minnesota"><name sortKey="Ryan, Charles J" sort="Ryan, Charles J" uniqKey="Ryan C" first="Charles J" last="Ryan">Charles J. 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