Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer
Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated t...
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| Veröffentlicht in: | PloS one 2015-08, Vol.10 (8), p.e0134731-e0134731 |
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| creator | Janjigian, Yelena Y Vakiani, Efsevia Ku, Geoffrey Y Herrera, Jessica M Tang, Laura H Bouvier, Nancy Viale, Agnès Socci, Nicholas D Capanu, Marinela Berger, Michael Ilson, David H |
| description | Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.
This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.
Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.
Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.
ClinicalTrials.gov NCT00917462. |
| doi_str_mv | 10.1371/journal.pone.0134731 |
| format | Article |
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This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.
Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.
Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.
ClinicalTrials.gov NCT00917462.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0134731</identifier><identifier>PMID: 26275293</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenocarcinoma - drug therapy ; Adenocarcinoma - mortality ; Adenocarcinoma - pathology ; Adult ; Aged ; Antineoplastic Agents - therapeutic use ; c-Met protein ; Cancer ; Cancer therapies ; Chemotherapy ; Dehydration ; Departments ; Disease-Free Survival ; Drug Resistance, Neoplasm - drug effects ; Enzyme inhibitors ; Esophageal cancer ; Esophageal Neoplasms - drug therapy ; Esophageal Neoplasms - mortality ; Esophageal Neoplasms - pathology ; Esophagogastric Junction - drug effects ; Esophagogastric Junction - pathology ; Esophagus ; Fatigue ; Female ; Gastric cancer ; Gene sequencing ; Genomes ; Humans ; Inhibitor drugs ; Kinases ; Male ; Medical prognosis ; Medicine ; Metastases ; Metastasis ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Niacinamide - analogs & derivatives ; Niacinamide - therapeutic use ; Oncology ; p53 Protein ; Pathology ; Patients ; Phenylurea Compounds - therapeutic use ; Platelet-derived growth factor ; Protein-tyrosine kinase ; Ret protein ; Skin ; Sorafenib ; Stomach cancer ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Survival ; Survival Analysis ; Toxicity ; Tumors ; Tyrosine ; Vascular endothelial growth factor</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0134731-e0134731</ispartof><rights>2015 Janjigian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Janjigian et al 2015 Janjigian et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-e0d50ee88067340b55dfbb3b272c81134b083253764a63d70b166acfc56b67413</citedby><cites>FETCH-LOGICAL-c526t-e0d50ee88067340b55dfbb3b272c81134b083253764a63d70b166acfc56b67413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537304/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537304/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26275293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stemmer, Salomon M</contributor><creatorcontrib>Janjigian, Yelena Y</creatorcontrib><creatorcontrib>Vakiani, Efsevia</creatorcontrib><creatorcontrib>Ku, Geoffrey Y</creatorcontrib><creatorcontrib>Herrera, Jessica M</creatorcontrib><creatorcontrib>Tang, Laura H</creatorcontrib><creatorcontrib>Bouvier, Nancy</creatorcontrib><creatorcontrib>Viale, Agnès</creatorcontrib><creatorcontrib>Socci, Nicholas D</creatorcontrib><creatorcontrib>Capanu, Marinela</creatorcontrib><creatorcontrib>Berger, Michael</creatorcontrib><creatorcontrib>Ilson, David H</creatorcontrib><title>Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.
This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.
Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.
Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.
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analogs & derivatives</subject><subject>Niacinamide - therapeutic use</subject><subject>Oncology</subject><subject>p53 Protein</subject><subject>Pathology</subject><subject>Patients</subject><subject>Phenylurea Compounds - therapeutic use</subject><subject>Platelet-derived growth factor</subject><subject>Protein-tyrosine kinase</subject><subject>Ret protein</subject><subject>Skin</subject><subject>Sorafenib</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Survival</subject><subject>Survival Analysis</subject><subject>Toxicity</subject><subject>Tumors</subject><subject>Tyrosine</subject><subject>Vascular endothelial growth factor</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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><sourceid>DOA</sourceid><recordid>eNptUk1vEzEUXCEQLYF_gMASl3JI8Mf6IxckFIUQVEQF5Wy99b7NbrWxg70B5c4PxyXb0iJOtp5nxm9GUxTPGZ0xodmbq7CPHvrZLnicUSZKLdiD4pTNBZ8qTsXDO_eT4klKV5RKYZR6XJxwxbXkc3Fa_LpoISFZr8ll7KAnoSFfQ4QGfVeRzpMLGDr0QyI_u6Elixa3YWgxwu5AvmATwQ0hHsgnHCANGerIMoVdCxvMWuBrssrzGPDv8Gy1fE0-7r0buuDJArzD-LR41ECf8Nl4Topv75eXiw_T88-r9eLd-dRJroYp0lpSRGOo0qKklZR1U1Wi4po7w3ICFTWCS6FVCUrUmlZMKXCNk6pSumRiUrw86u76kOwYYLJMU0mlKanIiPURUQe4srvYbSEebIDO_hmEuLEQs80erRa8oTVVUqp56UwJplbAG6Pnmps6hzsp3o6_7ast1i7HGKG_J3r_xXet3YQftswWBC2zwNkoEMP3PabBbrvksO_BY9iPezM6ZyZDX_0D_b-78ohyMaQUsbldhlF7Xaoblr0ulR1LlWkv7hq5Jd20SPwGo9fKDA</recordid><startdate>20150814</startdate><enddate>20150814</enddate><creator>Janjigian, Yelena Y</creator><creator>Vakiani, Efsevia</creator><creator>Ku, Geoffrey Y</creator><creator>Herrera, Jessica M</creator><creator>Tang, Laura H</creator><creator>Bouvier, Nancy</creator><creator>Viale, Agnès</creator><creator>Socci, Nicholas D</creator><creator>Capanu, Marinela</creator><creator>Berger, Michael</creator><creator>Ilson, David H</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</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>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150814</creationdate><title>Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer</title><author>Janjigian, Yelena Y ; Vakiani, Efsevia ; Ku, Geoffrey Y ; Herrera, Jessica M ; Tang, Laura H ; Bouvier, Nancy ; Viale, Agnès ; Socci, Nicholas D ; Capanu, Marinela ; Berger, Michael ; Ilson, David H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-e0d50ee88067340b55dfbb3b272c81134b083253764a63d70b166acfc56b67413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adenocarcinoma - drug therapy</topic><topic>Adenocarcinoma - mortality</topic><topic>Adenocarcinoma - pathology</topic><topic>Adult</topic><topic>Aged</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>c-Met protein</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Chemotherapy</topic><topic>Dehydration</topic><topic>Departments</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Enzyme inhibitors</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - drug therapy</topic><topic>Esophageal Neoplasms - mortality</topic><topic>Esophageal Neoplasms - pathology</topic><topic>Esophagogastric Junction - drug effects</topic><topic>Esophagogastric Junction - pathology</topic><topic>Esophagus</topic><topic>Fatigue</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>Gene sequencing</topic><topic>Genomes</topic><topic>Humans</topic><topic>Inhibitor drugs</topic><topic>Kinases</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Metastasis</topic><topic>Niacinamide - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Janjigian, Yelena Y</au><au>Vakiani, Efsevia</au><au>Ku, Geoffrey Y</au><au>Herrera, Jessica M</au><au>Tang, Laura H</au><au>Bouvier, Nancy</au><au>Viale, Agnès</au><au>Socci, Nicholas D</au><au>Capanu, Marinela</au><au>Berger, Michael</au><au>Ilson, David H</au><au>Stemmer, Salomon M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-14</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0134731</spage><epage>e0134731</epage><pages>e0134731-e0134731</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Vascular endothelial growth factor receptor (VEGFR2) directed therapies result in a modest survival benefit for patients with advanced esophageal and gastroesophageal (GE) junction cancer. Platelet-derived growth factor receptor (PDGFR) may contribute to escape from VEGFR2 inhibition. We evaluated the efficacy of sorafenib, a broad spectrum tyrosine kinase inhibitor targeting VEGFR2 and PDGFR as well as RET and RAF1, in patients with metastatic chemotherapy refractory esophageal and GE junction cancer.
This phase II trial of sorafenib 400 mg twice daily enrolled chemotherapy refractory patients with metastatic esophageal and GE junction cancer with primary endpoint of progression-free survival (PFS) rate at two months. Secondary endpoints included overall survival, objective response rate and toxicity.
Among 34 patients, 8 week Kaplan-Meier estimated PFS was 61% (90%CI 45 to 73%). Median PFS is 3.6 months (95% CI 1.8 to 3.9 months), with median overall survival OS 9.7 months (95% CI 5.9 to 11.6 months). Grade 3 toxicities were uncommon and included hand foot skin reaction, rash, dehydration and fatigue. One patient (3%) with ongoing complete response and remains on trial for over 5 years. Whole exome sequencing of this tumor revealed mutations in many cancer-associated genes including ARID1A, PIK3CA, and TP53, and focal amplifications of HMGA2 and MET.
Sorafenib therapy results in disease stabilization and encouraging PFS in patients with refractory esophageal and GE junction cancer.
ClinicalTrials.gov NCT00917462.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26275293</pmid><doi>10.1371/journal.pone.0134731</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1705058403 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenocarcinoma - drug therapy Adenocarcinoma - mortality Adenocarcinoma - pathology Adult Aged Antineoplastic Agents - therapeutic use c-Met protein Cancer Cancer therapies Chemotherapy Dehydration Departments Disease-Free Survival Drug Resistance, Neoplasm - drug effects Enzyme inhibitors Esophageal cancer Esophageal Neoplasms - drug therapy Esophageal Neoplasms - mortality Esophageal Neoplasms - pathology Esophagogastric Junction - drug effects Esophagogastric Junction - pathology Esophagus Fatigue Female Gastric cancer Gene sequencing Genomes Humans Inhibitor drugs Kinases Male Medical prognosis Medicine Metastases Metastasis Middle Aged Mutation Neoplasm Metastasis Niacinamide - analogs & derivatives Niacinamide - therapeutic use Oncology p53 Protein Pathology Patients Phenylurea Compounds - therapeutic use Platelet-derived growth factor Protein-tyrosine kinase Ret protein Skin Sorafenib Stomach cancer Stomach Neoplasms - drug therapy Stomach Neoplasms - mortality Stomach Neoplasms - pathology Survival Survival Analysis Toxicity Tumors Tyrosine Vascular endothelial growth factor |
| title | Phase II Trial of Sorafenib in Patients with Chemotherapy Refractory Metastatic Esophageal and Gastroesophageal (GE) Junction Cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-12T14%3A37%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Phase%20II%20Trial%20of%20Sorafenib%20in%20Patients%20with%20Chemotherapy%20Refractory%20Metastatic%20Esophageal%20and%20Gastroesophageal%20(GE)%20Junction%20Cancer&rft.jtitle=PloS%20one&rft.au=Janjigian,%20Yelena%20Y&rft.date=2015-08-14&rft.volume=10&rft.issue=8&rft.spage=e0134731&rft.epage=e0134731&rft.pages=e0134731-e0134731&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0134731&rft_dat=%3Cproquest_plos_%3E1705010918%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1705058403&rft_id=info:pmid/26275293&rft_doaj_id=oai_doaj_org_article_732f0d0655694c84a8d6a2f879728d29&rfr_iscdi=true |