Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
Identifieur interne : 002780 ( PubMed/Corpus ); précédent : 002779; suivant : 002781Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.
Auteurs : Toni K. Choueiri ; Bernard Escudier ; Thomas Powles ; Paul N. Mainwaring ; Brian I. Rini ; Frede Donskov ; Hans Hammers ; Thomas E. Hutson ; Jae-Lyun Lee ; Katriina Peltola ; Bruce J. Roth ; Georg A. Bjarnason ; Lajos Géczi ; Bhumsuk Keam ; Pablo Maroto ; Daniel Y C. Heng ; Manuela Schmidinger ; Philip W. Kantoff ; Anne Borgman-Hagey ; Colin Hessel ; Christian Scheffold ; Gisela M. Schwab ; Nizar M. Tannir ; Robert J. MotzerSource :
- The New England journal of medicine [ 1533-4406 ] ; 2015.
English descriptors
- KwdEn :
- Adult, Aged, Aged, 80 and over, Anilides (adverse effects), Anilides (therapeutic use), Antineoplastic Agents (adverse effects), Antineoplastic Agents (therapeutic use), Carcinoma, Renal Cell (drug therapy), Carcinoma, Renal Cell (mortality), Disease-Free Survival, Everolimus, Female, Humans, Kidney Neoplasms (drug therapy), Kidney Neoplasms (mortality), Male, Middle Aged, Pyridines (adverse effects), Pyridines (therapeutic use), Quality of Life, Sirolimus (adverse effects), Sirolimus (analogs & derivatives), Sirolimus (therapeutic use), Survival Analysis.
- MESH :
- chemical , adverse effects : Anilides, Antineoplastic Agents, Pyridines, Sirolimus.
- chemical , analogs & derivatives : Sirolimus.
- chemical , therapeutic use : Anilides, Antineoplastic Agents, Pyridines, Sirolimus.
- drug therapy : Carcinoma, Renal Cell, Kidney Neoplasms.
- mortality : Carcinoma, Renal Cell, Kidney Neoplasms.
- Adult, Aged, Aged, 80 and over, Disease-Free Survival, Everolimus, Female, Humans, Male, Middle Aged, Quality of Life, Survival Analysis.
Abstract
Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.
DOI: 10.1056/NEJMoa1510016
PubMed: 26406150
Links to Exploration step
pubmed:26406150Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.</title><author><name sortKey="Choueiri, Toni K" sort="Choueiri, Toni K" uniqKey="Choueiri T" first="Toni K" last="Choueiri">Toni K. Choueiri</name><affiliation><nlm:affiliation>From the Dana-Farber Cancer Institute, Boston (T.K.C., P.W.K.); Institut Gustave Roussy, Villejuif, France (B.E.); Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); Icon Cancer Care, South Brisbane, QLD, Australia (P.N.M.); Cleveland Clinic, Cleveland (B.I.R.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (H.H.); Texas Oncology-Charles A. Sammons Cancer Center, Baylor University, Dallas (T.E.H.); University of Ulsan College of Medicine (J.-L.L.) and Seoul National University Hospital (B.K.) - both in Seoul, South Korea; Helsinki University Central Hospital Cancer Center, Helsinki (K.P.); Washington University in St. Louis, St. Louis (B.J.R.); Sunnybrook Odette Cancer Centre, Toronto (G.A.B.), and Tom Baker Cancer Centre, Calgary, AB (D.Y.C.H.) - both in Canada; National Institute of Oncology, Budapest, Hungary (L.G.); Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.); Medical University of Vienna, Vienna (M.S.); Exelixis, South San Francisco, CA (A.B-H., C.H., C.S., G.M.S.); University of Texas M.D. Anderson Cancer Center, Houston (N.M.T.); and the Memorial Sloan Kettering Cancer Center, New York (R.J.M.).</nlm:affiliation></affiliation></author><author><name sortKey="Escudier, Bernard" sort="Escudier, Bernard" uniqKey="Escudier B" first="Bernard" last="Escudier">Bernard Escudier</name></author><author><name sortKey="Powles, Thomas" sort="Powles, Thomas" uniqKey="Powles T" first="Thomas" last="Powles">Thomas Powles</name></author><author><name sortKey="Mainwaring, Paul N" sort="Mainwaring, Paul N" uniqKey="Mainwaring P" first="Paul N" last="Mainwaring">Paul N. 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Schwab</name></author><author><name sortKey="Tannir, Nizar M" sort="Tannir, Nizar M" uniqKey="Tannir N" first="Nizar M" last="Tannir">Nizar M. Tannir</name></author><author><name sortKey="Motzer, Robert J" sort="Motzer, Robert J" uniqKey="Motzer R" first="Robert J" last="Motzer">Robert J. Motzer</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26406150</idno><idno type="pmid">26406150</idno><idno type="doi">10.1056/NEJMoa1510016</idno><idno type="wicri:Area/PubMed/Corpus">002780</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">002780</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.</title><author><name sortKey="Choueiri, Toni K" sort="Choueiri, Toni K" uniqKey="Choueiri T" first="Toni K" last="Choueiri">Toni K. Choueiri</name><affiliation><nlm:affiliation>From the Dana-Farber Cancer Institute, Boston (T.K.C., P.W.K.); Institut Gustave Roussy, Villejuif, France (B.E.); Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); Icon Cancer Care, South Brisbane, QLD, Australia (P.N.M.); Cleveland Clinic, Cleveland (B.I.R.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (H.H.); Texas Oncology-Charles A. Sammons Cancer Center, Baylor University, Dallas (T.E.H.); University of Ulsan College of Medicine (J.-L.L.) and Seoul National University Hospital (B.K.) - both in Seoul, South Korea; Helsinki University Central Hospital Cancer Center, Helsinki (K.P.); Washington University in St. Louis, St. Louis (B.J.R.); Sunnybrook Odette Cancer Centre, Toronto (G.A.B.), and Tom Baker Cancer Centre, Calgary, AB (D.Y.C.H.) - both in Canada; National Institute of Oncology, Budapest, Hungary (L.G.); Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.); Medical University of Vienna, Vienna (M.S.); Exelixis, South San Francisco, CA (A.B-H., C.H., C.S., G.M.S.); University of Texas M.D. Anderson Cancer Center, Houston (N.M.T.); and the Memorial Sloan Kettering Cancer Center, New York (R.J.M.).</nlm:affiliation></affiliation></author><author><name sortKey="Escudier, Bernard" sort="Escudier, Bernard" uniqKey="Escudier B" first="Bernard" last="Escudier">Bernard Escudier</name></author><author><name sortKey="Powles, Thomas" sort="Powles, Thomas" uniqKey="Powles T" first="Thomas" last="Powles">Thomas Powles</name></author><author><name sortKey="Mainwaring, Paul N" sort="Mainwaring, Paul N" uniqKey="Mainwaring P" first="Paul N" last="Mainwaring">Paul N. Mainwaring</name></author><author><name sortKey="Rini, Brian I" sort="Rini, Brian I" uniqKey="Rini B" first="Brian I" last="Rini">Brian I. Rini</name></author><author><name sortKey="Donskov, Frede" sort="Donskov, Frede" uniqKey="Donskov F" first="Frede" last="Donskov">Frede Donskov</name></author><author><name sortKey="Hammers, Hans" sort="Hammers, Hans" uniqKey="Hammers H" first="Hans" last="Hammers">Hans Hammers</name></author><author><name sortKey="Hutson, Thomas E" sort="Hutson, Thomas E" uniqKey="Hutson T" first="Thomas E" last="Hutson">Thomas E. Hutson</name></author><author><name sortKey="Lee, Jae Lyun" sort="Lee, Jae Lyun" uniqKey="Lee J" first="Jae-Lyun" last="Lee">Jae-Lyun Lee</name></author><author><name sortKey="Peltola, Katriina" sort="Peltola, Katriina" uniqKey="Peltola K" first="Katriina" last="Peltola">Katriina Peltola</name></author><author><name sortKey="Roth, Bruce J" sort="Roth, Bruce J" uniqKey="Roth B" first="Bruce J" last="Roth">Bruce J. Roth</name></author><author><name sortKey="Bjarnason, Georg A" sort="Bjarnason, Georg A" uniqKey="Bjarnason G" first="Georg A" last="Bjarnason">Georg A. Bjarnason</name></author><author><name sortKey="Geczi, Lajos" sort="Geczi, Lajos" uniqKey="Geczi L" first="Lajos" last="Géczi">Lajos Géczi</name></author><author><name sortKey="Keam, Bhumsuk" sort="Keam, Bhumsuk" uniqKey="Keam B" first="Bhumsuk" last="Keam">Bhumsuk Keam</name></author><author><name sortKey="Maroto, Pablo" sort="Maroto, Pablo" uniqKey="Maroto P" first="Pablo" last="Maroto">Pablo Maroto</name></author><author><name sortKey="Heng, Daniel Y C" sort="Heng, Daniel Y C" uniqKey="Heng D" first="Daniel Y C" last="Heng">Daniel Y C. Heng</name></author><author><name sortKey="Schmidinger, Manuela" sort="Schmidinger, Manuela" uniqKey="Schmidinger M" first="Manuela" last="Schmidinger">Manuela Schmidinger</name></author><author><name sortKey="Kantoff, Philip W" sort="Kantoff, Philip W" uniqKey="Kantoff P" first="Philip W" last="Kantoff">Philip W. Kantoff</name></author><author><name sortKey="Borgman Hagey, Anne" sort="Borgman Hagey, Anne" uniqKey="Borgman Hagey A" first="Anne" last="Borgman-Hagey">Anne Borgman-Hagey</name></author><author><name sortKey="Hessel, Colin" sort="Hessel, Colin" uniqKey="Hessel C" first="Colin" last="Hessel">Colin Hessel</name></author><author><name sortKey="Scheffold, Christian" sort="Scheffold, Christian" uniqKey="Scheffold C" first="Christian" last="Scheffold">Christian Scheffold</name></author><author><name sortKey="Schwab, Gisela M" sort="Schwab, Gisela M" uniqKey="Schwab G" first="Gisela M" last="Schwab">Gisela M. Schwab</name></author><author><name sortKey="Tannir, Nizar M" sort="Tannir, Nizar M" uniqKey="Tannir N" first="Nizar M" last="Tannir">Nizar M. Tannir</name></author><author><name sortKey="Motzer, Robert J" sort="Motzer, Robert J" uniqKey="Motzer R" first="Robert J" last="Motzer">Robert J. Motzer</name></author></analytic><series><title level="j">The New England journal of medicine</title><idno type="eISSN">1533-4406</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Anilides (adverse effects)</term><term>Anilides (therapeutic use)</term><term>Antineoplastic Agents (adverse effects)</term><term>Antineoplastic Agents (therapeutic use)</term><term>Carcinoma, Renal Cell (drug therapy)</term><term>Carcinoma, Renal Cell (mortality)</term><term>Disease-Free Survival</term><term>Everolimus</term><term>Female</term><term>Humans</term><term>Kidney Neoplasms (drug therapy)</term><term>Kidney Neoplasms (mortality)</term><term>Male</term><term>Middle Aged</term><term>Pyridines (adverse effects)</term><term>Pyridines (therapeutic use)</term><term>Quality of Life</term><term>Sirolimus (adverse effects)</term><term>Sirolimus (analogs & derivatives)</term><term>Sirolimus (therapeutic use)</term><term>Survival Analysis</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anilides</term><term>Antineoplastic Agents</term><term>Pyridines</term><term>Sirolimus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Sirolimus</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anilides</term><term>Antineoplastic Agents</term><term>Pyridines</term><term>Sirolimus</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Carcinoma, Renal Cell</term><term>Kidney Neoplasms</term></keywords><keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Carcinoma, Renal Cell</term><term>Kidney Neoplasms</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Adult</term><term>Aged</term><term>Aged, 80 and over</term><term>Disease-Free Survival</term><term>Everolimus</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Quality of Life</term><term>Survival Analysis</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">26406150</PMID><DateCreated><Year>2015</Year><Month>11</Month><Day>05</Day></DateCreated><DateCompleted><Year>2015</Year><Month>11</Month><Day>12</Day></DateCompleted><DateRevised><Year>2017</Year><Month>09</Month><Day>30</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1533-4406</ISSN><JournalIssue CitedMedium="Internet"><Volume>373</Volume><Issue>19</Issue><PubDate><Year>2015</Year><Month>Nov</Month><Day>05</Day></PubDate></JournalIssue><Title>The New England journal of medicine</Title><ISOAbbreviation>N. Engl. J. Med.</ISOAbbreviation></Journal><ArticleTitle>Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma.</ArticleTitle><Pagination><MedlinePgn>1814-23</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1056/NEJMoa1510016</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Cabozantinib is an oral, small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) as well as MET and AXL, each of which has been implicated in the pathobiology of metastatic renal-cell carcinoma or in the development of resistance to antiangiogenic drugs. This randomized, open-label, phase 3 trial evaluated the efficacy of cabozantinib, as compared with everolimus, in patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">We randomly assigned 658 patients to receive cabozantinib at a dose of 60 mg daily or everolimus at a dose of 10 mg daily. The primary end point was progression-free survival. Secondary efficacy end points were overall survival and objective response rate.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Median progression-free survival was 7.4 months with cabozantinib and 3.8 months with everolimus. The rate of progression or death was 42% lower with cabozantinib than with everolimus (hazard ratio, 0.58; 95% confidence interval [CI] 0.45 to 0.75; P<0.001). The objective response rate was 21% with cabozantinib and 5% with everolimus (P<0.001). A planned interim analysis showed that overall survival was longer with cabozantinib than with everolimus (hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005) but did not cross the significance boundary for the interim analysis. Adverse events were managed with dose reductions; doses were reduced in 60% of the patients who received cabozantinib and in 25% of those who received everolimus. Discontinuation of study treatment owing to adverse events occurred in 9% of the patients who received cabozantinib and in 10% of those who received everolimus.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Progression-free survival was longer with cabozantinib than with everolimus among patients with renal-cell carcinoma that had progressed after VEGFR-targeted therapy. (Funded by Exelixis; METEOR ClinicalTrials.gov number, NCT01865747.).</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Choueiri</LastName><ForeName>Toni K</ForeName><Initials>TK</Initials><AffiliationInfo><Affiliation>From the Dana-Farber Cancer Institute, Boston (T.K.C., P.W.K.); Institut Gustave Roussy, Villejuif, France (B.E.); Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free NHS Trust, London (T.P.); Icon Cancer Care, South Brisbane, QLD, Australia (P.N.M.); Cleveland Clinic, Cleveland (B.I.R.); Aarhus University Hospital, Aarhus, Denmark (F.D.); Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore (H.H.); Texas Oncology-Charles A. Sammons Cancer Center, Baylor University, Dallas (T.E.H.); University of Ulsan College of Medicine (J.-L.L.) and Seoul National University Hospital (B.K.) - both in Seoul, South Korea; Helsinki University Central Hospital Cancer Center, Helsinki (K.P.); Washington University in St. Louis, St. Louis (B.J.R.); Sunnybrook Odette Cancer Centre, Toronto (G.A.B.), and Tom Baker Cancer Centre, Calgary, AB (D.Y.C.H.) - both in Canada; National Institute of Oncology, Budapest, Hungary (L.G.); Hospital de la Santa Creu i Sant Pau, Barcelona (P.M.); Medical University of Vienna, Vienna (M.S.); Exelixis, South San Francisco, CA (A.B-H., C.H., C.S., G.M.S.); University of Texas M.D. Anderson Cancer Center, Houston (N.M.T.); and the Memorial Sloan Kettering Cancer Center, New York (R.J.M.).</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Escudier</LastName><ForeName>Bernard</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Powles</LastName><ForeName>Thomas</ForeName><Initials>T</Initials></Author><Author ValidYN="Y"><LastName>Mainwaring</LastName><ForeName>Paul N</ForeName><Initials>PN</Initials></Author><Author ValidYN="Y"><LastName>Rini</LastName><ForeName>Brian I</ForeName><Initials>BI</Initials></Author><Author ValidYN="Y"><LastName>Donskov</LastName><ForeName>Frede</ForeName><Initials>F</Initials></Author><Author ValidYN="Y"><LastName>Hammers</LastName><ForeName>Hans</ForeName><Initials>H</Initials></Author><Author ValidYN="Y"><LastName>Hutson</LastName><ForeName>Thomas E</ForeName><Initials>TE</Initials></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Jae-Lyun</ForeName><Initials>JL</Initials></Author><Author ValidYN="Y"><LastName>Peltola</LastName><ForeName>Katriina</ForeName><Initials>K</Initials></Author><Author ValidYN="Y"><LastName>Roth</LastName><ForeName>Bruce J</ForeName><Initials>BJ</Initials></Author><Author ValidYN="Y"><LastName>Bjarnason</LastName><ForeName>Georg A</ForeName><Initials>GA</Initials></Author><Author ValidYN="Y"><LastName>Géczi</LastName><ForeName>Lajos</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Keam</LastName><ForeName>Bhumsuk</ForeName><Initials>B</Initials></Author><Author ValidYN="Y"><LastName>Maroto</LastName><ForeName>Pablo</ForeName><Initials>P</Initials></Author><Author ValidYN="Y"><LastName>Heng</LastName><ForeName>Daniel Y C</ForeName><Initials>DY</Initials></Author><Author ValidYN="Y"><LastName>Schmidinger</LastName><ForeName>Manuela</ForeName><Initials>M</Initials></Author><Author ValidYN="Y"><LastName>Kantoff</LastName><ForeName>Philip W</ForeName><Initials>PW</Initials></Author><Author ValidYN="Y"><LastName>Borgman-Hagey</LastName><ForeName>Anne</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Hessel</LastName><ForeName>Colin</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Scheffold</LastName><ForeName>Christian</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Schwab</LastName><ForeName>Gisela M</ForeName><Initials>GM</Initials></Author><Author ValidYN="Y"><LastName>Tannir</LastName><ForeName>Nizar M</ForeName><Initials>NM</Initials></Author><Author ValidYN="Y"><LastName>Motzer</LastName><ForeName>Robert J</ForeName><Initials>RJ</Initials></Author><Author ValidYN="Y"><CollectiveName>METEOR Investigators</CollectiveName></Author></AuthorList><Language>eng</Language><DataBankList CompleteYN="Y"><DataBank><DataBankName>ClinicalTrials.gov</DataBankName><AccessionNumberList><AccessionNumber>NCT01865747</AccessionNumber></AccessionNumberList></DataBank></DataBankList><GrantList CompleteYN="Y"><Grant><GrantID>P30 CA008748</GrantID><Acronym>CA</Acronym><Agency>NCI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D016448">Multicenter Study</PublicationType><PublicationType UI="D016449">Randomized Controlled Trial</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2015</Year><Month>09</Month><Day>25</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>N Engl J Med</MedlineTA><NlmUniqueID>0255562</NlmUniqueID><ISSNLinking>0028-4793</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000813">Anilides</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000970">Antineoplastic Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance 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