A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-04

AUTHORS

Evan Y. Yu, Susan L. Ellard, Sebastien J. Hotte, Joel R. Gingerich, Anthony M. Joshua, Martin E. Gleave, Kim N. Chi

ABSTRACT

Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC). Experimental design Eligible patients were randomized 1:1 to receive intravenous apatorsen (3 loading doses of 600 mg within 5-9 days followed by weekly doses of 1000 mg) with oral prednisone 5 mg twice daily or prednisone alone. The primary endpoint was disease progression at 12 weeks. Crossover from prednisone alone was allowed after radiographic progression. Results 74 patients received apatorsen + prednisone (n = 36) or prednisone alone (n = 38). Twenty-five patients crossed-over to receive apatorsen + prednisone. Apatorsen treated patients received a median of 19 infusions. 50% of apatorsen + prednisone patients (95% CI: 32.9%, 67.1%) compared with 42% of prednisone patients (95% CI: 26.3%, 59.2%) did not have disease progression at week 12 (P = 0.33). A PSA decline of ≥50% was observed in 47% of apatorsen + prednisone and 24% of prednisone patients (P = 0.04), with a median duration of response of 24.1 weeks (95% CI: 12.0, 52) and 14.0 weeks (95% CI: 4.0, 44.4), respectively. A PSA decline of ≥50% was observed in 5 patients (20%) that received cross-over apatorsen. Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients. Conclusions Apatorsen + prednisone did not change the proportion of CRPC patients without disease progression at 12 weeks compared to prednisone but was associated with significant PSA declines. Further evaluation of Hsp27 targeting in prostate cancer is warranted. More... »

PAGES

278-287

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10637-017-0553-x

DOI

http://dx.doi.org/10.1007/s10637-017-0553-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1099696160

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29250742


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adult", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Aged, 80 and over", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Dose-Response Relationship, Drug", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Endpoint Determination", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "HSP27 Heat-Shock Proteins", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neoplasm Metastasis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Oligonucleotides", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Oligonucleotides, Antisense", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prednisone", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prostate-Specific Antigen", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Prostatic Neoplasms, Castration-Resistant", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Treatment Outcome", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Fred Hutchinson Cancer Research Center", 
          "id": "https://www.grid.ac/institutes/grid.270240.3", 
          "name": [
            "Division of Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA", 
            "Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Yu", 
        "givenName": "Evan Y.", 
        "id": "sg:person.01362673754.96", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362673754.96"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of British Columbia", 
          "id": "https://www.grid.ac/institutes/grid.17091.3e", 
          "name": [
            "Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ellard", 
        "givenName": "Susan L.", 
        "id": "sg:person.01004224136.10", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004224136.10"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "McMaster University", 
          "id": "https://www.grid.ac/institutes/grid.25073.33", 
          "name": [
            "Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, ON, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hotte", 
        "givenName": "Sebastien J.", 
        "id": "sg:person.01116377030.40", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01116377030.40"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Manitoba", 
          "id": "https://www.grid.ac/institutes/grid.21613.37", 
          "name": [
            "Division of Medical Oncology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gingerich", 
        "givenName": "Joel R.", 
        "id": "sg:person.012002412373.25", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002412373.25"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Princess Margaret Cancer Centre", 
          "id": "https://www.grid.ac/institutes/grid.415224.4", 
          "name": [
            "Kinghorn Cancer Center, St Vincents Hospital, Sydney, NSW, Australia", 
            "Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia", 
            "Princess Margaret Cancer Centre, Toronto, ON, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Joshua", 
        "givenName": "Anthony M.", 
        "id": "sg:person.0774245543.30", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0774245543.30"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of British Columbia", 
          "id": "https://www.grid.ac/institutes/grid.17091.3e", 
          "name": [
            "Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gleave", 
        "givenName": "Martin E.", 
        "id": "sg:person.01147006714.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01147006714.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "BC Cancer Agency", 
          "id": "https://www.grid.ac/institutes/grid.248762.d", 
          "name": [
            "Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada", 
            "BC Cancer Agency, 600 West 10th Avenue, V5Z 4E6, Vancouver, BC, Canada"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chi", 
        "givenName": "Kim N.", 
        "id": "sg:person.01142252161.65", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142252161.65"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/bjc.2012.188", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005100559", 
          "https://doi.org/10.1038/bjc.2012.188"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203850", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006576068", 
          "https://doi.org/10.1038/sj.onc.1203850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1203850", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006576068", 
          "https://doi.org/10.1038/sj.onc.1203850"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ucl.2012.07.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1006946081"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-12-3979", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007149037"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-07-2057", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011079005"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1535-7163.mct-06-0417", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1013174688"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3322/caac.21387", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014894112"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-05-1840", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015931265"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3727/000000001783992605", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021421883"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3727/000000001783992605", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021421883"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cncr.25599", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022395196"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ejca.2008.10.026", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1026558254"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1074/jbc.m303417200", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028556186"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2007.12.4487", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1031178629"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/0008-5472.can-03-3998", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049988670"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0197-2456(89)90015-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053744925"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/0197-2456(89)90015-9", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053744925"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/annonc/mdw068", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059394690"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2015.64.2702", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1064204460"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1379/csc-99r.1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067174002", 
          "https://doi.org/10.1379/csc-99r.1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1379/csc-99r.1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1067174002", 
          "https://doi.org/10.1379/csc-99r.1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/cc.2.6.521", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072296833"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1078569379", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1082711051", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2017.35.6_suppl.289", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1084254973"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-04", 
    "datePublishedReg": "2018-04-01", 
    "description": "Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC). Experimental design Eligible patients were randomized 1:1 to receive intravenous apatorsen (3 loading doses of 600\u00a0mg within 5-9\u00a0days followed by weekly doses of 1000\u00a0mg) with oral prednisone 5\u00a0mg twice daily or prednisone alone. The primary endpoint was disease progression at 12\u00a0weeks. Crossover from prednisone alone was allowed after radiographic progression. Results 74 patients received apatorsen\u2009+\u2009prednisone (n\u2009=\u200936) or prednisone alone (n\u2009=\u200938). Twenty-five patients crossed-over to receive apatorsen\u2009+\u2009prednisone. Apatorsen treated patients received a median of 19 infusions. 50% of apatorsen\u2009+\u2009prednisone patients (95% CI: 32.9%, 67.1%) compared with 42% of prednisone patients (95% CI: 26.3%, 59.2%) did not have disease progression at week 12 (P\u2009=\u20090.33). A PSA decline of \u226550% was observed in 47% of apatorsen\u2009+\u2009prednisone and 24% of prednisone patients (P\u2009=\u20090.04), with a median duration of response of 24.1\u00a0weeks (95% CI: 12.0, 52) and 14.0\u00a0weeks (95% CI: 4.0, 44.4), respectively. A PSA decline of \u226550% was observed in 5 patients (20%) that received cross-over apatorsen. Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients. Conclusions Apatorsen\u2009+\u2009prednisone did not change the proportion of CRPC patients without disease progression at 12\u00a0weeks compared to prednisone but was associated with significant PSA declines. Further evaluation of Hsp27 targeting in prostate cancer is warranted.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s10637-017-0553-x", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1094201", 
        "issn": [
          "0167-6997", 
          "1573-0646"
        ], 
        "name": "Investigational New Drugs", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "2", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "36"
      }
    ], 
    "name": "A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer", 
    "pagination": "278-287", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "5c8d6c2db7946576d0f8ef55a71c223ce1005c830d96c2798e4d9cbb59aae371"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29250742"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "8309330"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s10637-017-0553-x"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1099696160"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s10637-017-0553-x", 
      "https://app.dimensions.ai/details/publication/pub.1099696160"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T11:03", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000352_0000000352/records_60354_00000003.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://link.springer.com/10.1007%2Fs10637-017-0553-x"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s10637-017-0553-x'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s10637-017-0553-x'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s10637-017-0553-x'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s10637-017-0553-x'


 

This table displays all metadata directly associated to this object as RDF triples.

262 TRIPLES      21 PREDICATES      67 URIs      37 LITERALS      25 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s10637-017-0553-x schema:about N033e78b1ce414c40a1e48a1436d7390e
2 N3e9ed54f86e047b1b25050c74edd26bb
3 N61225f992cb1468c8c6bf7ae7b0da5e7
4 N79521f0d67ea4994ae89e49788e1980b
5 N7a1481881e8848f7a0ad516dae85ca1b
6 Na0ab3710dba64152b30aa2b1cfba61a8
7 Na9a8760d399d45e39e2d09db7e352367
8 Naaa1cf35100a4ab6b7cd91ae5ef6044f
9 Nb3010603ebea4649979021a522127667
10 Nb3c25e6280bc414d803013d8424578cd
11 Nbe5f1d9f905b48ab8978b8f885b9069b
12 Nbf6841fa6df3442091a9de53f72d72b0
13 Ncba27bd2edfe4c329a64a53881028fcb
14 Ndc8553661566460b9ebe62690f08cb79
15 Nee9062987ada45bfa90df957df8af1d4
16 Nfa3113d3165e4f1da0d65c3af9f10a1b
17 anzsrc-for:11
18 anzsrc-for:1112
19 schema:author N8f8a2f0e8ef24837a7749ad06d506cf3
20 schema:citation sg:pub.10.1038/bjc.2012.188
21 sg:pub.10.1038/sj.onc.1203850
22 sg:pub.10.1379/csc-99r.1
23 https://app.dimensions.ai/details/publication/pub.1078569379
24 https://app.dimensions.ai/details/publication/pub.1082711051
25 https://doi.org/10.1002/cncr.25599
26 https://doi.org/10.1016/0197-2456(89)90015-9
27 https://doi.org/10.1016/j.ejca.2008.10.026
28 https://doi.org/10.1016/j.ucl.2012.07.011
29 https://doi.org/10.1074/jbc.m303417200
30 https://doi.org/10.1093/annonc/mdw068
31 https://doi.org/10.1158/0008-5472.can-03-3998
32 https://doi.org/10.1158/0008-5472.can-05-1840
33 https://doi.org/10.1158/0008-5472.can-07-2057
34 https://doi.org/10.1158/0008-5472.can-12-3979
35 https://doi.org/10.1158/1535-7163.mct-06-0417
36 https://doi.org/10.1200/jco.2007.12.4487
37 https://doi.org/10.1200/jco.2015.64.2702
38 https://doi.org/10.1200/jco.2017.35.6_suppl.289
39 https://doi.org/10.3322/caac.21387
40 https://doi.org/10.3727/000000001783992605
41 https://doi.org/10.4161/cc.2.6.521
42 schema:datePublished 2018-04
43 schema:datePublishedReg 2018-04-01
44 schema:description Purpose Heat shock protein 27 (Hsp27) is implicated in prostate cancer progression. Apatorsen is a second generation phosphorothioate antisense inhibitor of Hsp27 expression. We evaluated apatorsen in patients with metastatic castration resistant prostate cancer (mCRPC). Experimental design Eligible patients were randomized 1:1 to receive intravenous apatorsen (3 loading doses of 600 mg within 5-9 days followed by weekly doses of 1000 mg) with oral prednisone 5 mg twice daily or prednisone alone. The primary endpoint was disease progression at 12 weeks. Crossover from prednisone alone was allowed after radiographic progression. Results 74 patients received apatorsen + prednisone (n = 36) or prednisone alone (n = 38). Twenty-five patients crossed-over to receive apatorsen + prednisone. Apatorsen treated patients received a median of 19 infusions. 50% of apatorsen + prednisone patients (95% CI: 32.9%, 67.1%) compared with 42% of prednisone patients (95% CI: 26.3%, 59.2%) did not have disease progression at week 12 (P = 0.33). A PSA decline of ≥50% was observed in 47% of apatorsen + prednisone and 24% of prednisone patients (P = 0.04), with a median duration of response of 24.1 weeks (95% CI: 12.0, 52) and 14.0 weeks (95% CI: 4.0, 44.4), respectively. A PSA decline of ≥50% was observed in 5 patients (20%) that received cross-over apatorsen. Infusion reactions were the most commonly reported adverse event occurring in 77% of apatorsen-treated patients. Conclusions Apatorsen + prednisone did not change the proportion of CRPC patients without disease progression at 12 weeks compared to prednisone but was associated with significant PSA declines. Further evaluation of Hsp27 targeting in prostate cancer is warranted.
45 schema:genre research_article
46 schema:inLanguage en
47 schema:isAccessibleForFree false
48 schema:isPartOf N759ca85ad5b04fe18624ee4b288cf30f
49 N94a87b6631f943d69ee2de4248e46d28
50 sg:journal.1094201
51 schema:name A randomized phase 2 study of a HSP27 targeting antisense, apatorsen with prednisone versus prednisone alone, in patients with metastatic castration resistant prostate cancer
52 schema:pagination 278-287
53 schema:productId N06e6fcc886814304b7a393fa5b0077ed
54 N11a35341ec61488dbbcc46131059c934
55 N1f0be026c8f244008eb6e2a0b6caa48a
56 N5c462216e63c4621800ab00191354d55
57 Ne3aaf89eb5de4f7792cbb78febf939b2
58 schema:sameAs https://app.dimensions.ai/details/publication/pub.1099696160
59 https://doi.org/10.1007/s10637-017-0553-x
60 schema:sdDatePublished 2019-04-11T11:03
61 schema:sdLicense https://scigraph.springernature.com/explorer/license/
62 schema:sdPublisher Ncbce3feccfa14cafa256a0fc11fedb21
63 schema:url https://link.springer.com/10.1007%2Fs10637-017-0553-x
64 sgo:license sg:explorer/license/
65 sgo:sdDataset articles
66 rdf:type schema:ScholarlyArticle
67 N033e78b1ce414c40a1e48a1436d7390e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
68 schema:name Prostatic Neoplasms, Castration-Resistant
69 rdf:type schema:DefinedTerm
70 N046aaab6b8374ec7b6fed33a9d1d47b2 rdf:first sg:person.012002412373.25
71 rdf:rest N0fc3d03072434b46b31681e927abf7bd
72 N06e6fcc886814304b7a393fa5b0077ed schema:name readcube_id
73 schema:value 5c8d6c2db7946576d0f8ef55a71c223ce1005c830d96c2798e4d9cbb59aae371
74 rdf:type schema:PropertyValue
75 N0fc3d03072434b46b31681e927abf7bd rdf:first sg:person.0774245543.30
76 rdf:rest Nbf5e3ffcb2f5420eabf4f8b398635d63
77 N11a35341ec61488dbbcc46131059c934 schema:name dimensions_id
78 schema:value pub.1099696160
79 rdf:type schema:PropertyValue
80 N13e2b5f41f304014a0bd2f194868a5a0 rdf:first sg:person.01116377030.40
81 rdf:rest N046aaab6b8374ec7b6fed33a9d1d47b2
82 N1f0be026c8f244008eb6e2a0b6caa48a schema:name nlm_unique_id
83 schema:value 8309330
84 rdf:type schema:PropertyValue
85 N20d89f64b9d44a2aad6858aa79a84383 rdf:first sg:person.01142252161.65
86 rdf:rest rdf:nil
87 N3e9ed54f86e047b1b25050c74edd26bb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
88 schema:name Adult
89 rdf:type schema:DefinedTerm
90 N5c462216e63c4621800ab00191354d55 schema:name pubmed_id
91 schema:value 29250742
92 rdf:type schema:PropertyValue
93 N61225f992cb1468c8c6bf7ae7b0da5e7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
94 schema:name Dose-Response Relationship, Drug
95 rdf:type schema:DefinedTerm
96 N759ca85ad5b04fe18624ee4b288cf30f schema:issueNumber 2
97 rdf:type schema:PublicationIssue
98 N79521f0d67ea4994ae89e49788e1980b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
99 schema:name HSP27 Heat-Shock Proteins
100 rdf:type schema:DefinedTerm
101 N7a1481881e8848f7a0ad516dae85ca1b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
102 schema:name Endpoint Determination
103 rdf:type schema:DefinedTerm
104 N8f8a2f0e8ef24837a7749ad06d506cf3 rdf:first sg:person.01362673754.96
105 rdf:rest Na0617d50d2a44db89617d8b32d88738f
106 N94a87b6631f943d69ee2de4248e46d28 schema:volumeNumber 36
107 rdf:type schema:PublicationVolume
108 Na0617d50d2a44db89617d8b32d88738f rdf:first sg:person.01004224136.10
109 rdf:rest N13e2b5f41f304014a0bd2f194868a5a0
110 Na0ab3710dba64152b30aa2b1cfba61a8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
111 schema:name Male
112 rdf:type schema:DefinedTerm
113 Na9a8760d399d45e39e2d09db7e352367 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
114 schema:name Aged
115 rdf:type schema:DefinedTerm
116 Naaa1cf35100a4ab6b7cd91ae5ef6044f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
117 schema:name Neoplasm Metastasis
118 rdf:type schema:DefinedTerm
119 Nb3010603ebea4649979021a522127667 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
120 schema:name Treatment Outcome
121 rdf:type schema:DefinedTerm
122 Nb3c25e6280bc414d803013d8424578cd schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
123 schema:name Middle Aged
124 rdf:type schema:DefinedTerm
125 Nbe5f1d9f905b48ab8978b8f885b9069b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
126 schema:name Aged, 80 and over
127 rdf:type schema:DefinedTerm
128 Nbf5e3ffcb2f5420eabf4f8b398635d63 rdf:first sg:person.01147006714.34
129 rdf:rest N20d89f64b9d44a2aad6858aa79a84383
130 Nbf6841fa6df3442091a9de53f72d72b0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
131 schema:name Prostate-Specific Antigen
132 rdf:type schema:DefinedTerm
133 Ncba27bd2edfe4c329a64a53881028fcb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Humans
135 rdf:type schema:DefinedTerm
136 Ncbce3feccfa14cafa256a0fc11fedb21 schema:name Springer Nature - SN SciGraph project
137 rdf:type schema:Organization
138 Ndc8553661566460b9ebe62690f08cb79 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
139 schema:name Prednisone
140 rdf:type schema:DefinedTerm
141 Ne3aaf89eb5de4f7792cbb78febf939b2 schema:name doi
142 schema:value 10.1007/s10637-017-0553-x
143 rdf:type schema:PropertyValue
144 Nee9062987ada45bfa90df957df8af1d4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
145 schema:name Oligonucleotides, Antisense
146 rdf:type schema:DefinedTerm
147 Nfa3113d3165e4f1da0d65c3af9f10a1b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Oligonucleotides
149 rdf:type schema:DefinedTerm
150 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
151 schema:name Medical and Health Sciences
152 rdf:type schema:DefinedTerm
153 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
154 schema:name Oncology and Carcinogenesis
155 rdf:type schema:DefinedTerm
156 sg:journal.1094201 schema:issn 0167-6997
157 1573-0646
158 schema:name Investigational New Drugs
159 rdf:type schema:Periodical
160 sg:person.01004224136.10 schema:affiliation https://www.grid.ac/institutes/grid.17091.3e
161 schema:familyName Ellard
162 schema:givenName Susan L.
163 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01004224136.10
164 rdf:type schema:Person
165 sg:person.01116377030.40 schema:affiliation https://www.grid.ac/institutes/grid.25073.33
166 schema:familyName Hotte
167 schema:givenName Sebastien J.
168 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01116377030.40
169 rdf:type schema:Person
170 sg:person.01142252161.65 schema:affiliation https://www.grid.ac/institutes/grid.248762.d
171 schema:familyName Chi
172 schema:givenName Kim N.
173 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01142252161.65
174 rdf:type schema:Person
175 sg:person.01147006714.34 schema:affiliation https://www.grid.ac/institutes/grid.17091.3e
176 schema:familyName Gleave
177 schema:givenName Martin E.
178 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01147006714.34
179 rdf:type schema:Person
180 sg:person.012002412373.25 schema:affiliation https://www.grid.ac/institutes/grid.21613.37
181 schema:familyName Gingerich
182 schema:givenName Joel R.
183 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012002412373.25
184 rdf:type schema:Person
185 sg:person.01362673754.96 schema:affiliation https://www.grid.ac/institutes/grid.270240.3
186 schema:familyName Yu
187 schema:givenName Evan Y.
188 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362673754.96
189 rdf:type schema:Person
190 sg:person.0774245543.30 schema:affiliation https://www.grid.ac/institutes/grid.415224.4
191 schema:familyName Joshua
192 schema:givenName Anthony M.
193 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0774245543.30
194 rdf:type schema:Person
195 sg:pub.10.1038/bjc.2012.188 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005100559
196 https://doi.org/10.1038/bjc.2012.188
197 rdf:type schema:CreativeWork
198 sg:pub.10.1038/sj.onc.1203850 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006576068
199 https://doi.org/10.1038/sj.onc.1203850
200 rdf:type schema:CreativeWork
201 sg:pub.10.1379/csc-99r.1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1067174002
202 https://doi.org/10.1379/csc-99r.1
203 rdf:type schema:CreativeWork
204 https://app.dimensions.ai/details/publication/pub.1078569379 schema:CreativeWork
205 https://app.dimensions.ai/details/publication/pub.1082711051 schema:CreativeWork
206 https://doi.org/10.1002/cncr.25599 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022395196
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1016/0197-2456(89)90015-9 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053744925
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1016/j.ejca.2008.10.026 schema:sameAs https://app.dimensions.ai/details/publication/pub.1026558254
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1016/j.ucl.2012.07.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1006946081
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1074/jbc.m303417200 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028556186
215 rdf:type schema:CreativeWork
216 https://doi.org/10.1093/annonc/mdw068 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059394690
217 rdf:type schema:CreativeWork
218 https://doi.org/10.1158/0008-5472.can-03-3998 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049988670
219 rdf:type schema:CreativeWork
220 https://doi.org/10.1158/0008-5472.can-05-1840 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015931265
221 rdf:type schema:CreativeWork
222 https://doi.org/10.1158/0008-5472.can-07-2057 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011079005
223 rdf:type schema:CreativeWork
224 https://doi.org/10.1158/0008-5472.can-12-3979 schema:sameAs https://app.dimensions.ai/details/publication/pub.1007149037
225 rdf:type schema:CreativeWork
226 https://doi.org/10.1158/1535-7163.mct-06-0417 schema:sameAs https://app.dimensions.ai/details/publication/pub.1013174688
227 rdf:type schema:CreativeWork
228 https://doi.org/10.1200/jco.2007.12.4487 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031178629
229 rdf:type schema:CreativeWork
230 https://doi.org/10.1200/jco.2015.64.2702 schema:sameAs https://app.dimensions.ai/details/publication/pub.1064204460
231 rdf:type schema:CreativeWork
232 https://doi.org/10.1200/jco.2017.35.6_suppl.289 schema:sameAs https://app.dimensions.ai/details/publication/pub.1084254973
233 rdf:type schema:CreativeWork
234 https://doi.org/10.3322/caac.21387 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014894112
235 rdf:type schema:CreativeWork
236 https://doi.org/10.3727/000000001783992605 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021421883
237 rdf:type schema:CreativeWork
238 https://doi.org/10.4161/cc.2.6.521 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072296833
239 rdf:type schema:CreativeWork
240 https://www.grid.ac/institutes/grid.17091.3e schema:alternateName University of British Columbia
241 schema:name Department of Urologic Sciences, Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
242 Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
243 rdf:type schema:Organization
244 https://www.grid.ac/institutes/grid.21613.37 schema:alternateName University of Manitoba
245 schema:name Division of Medical Oncology, Cancer Care Manitoba, University of Manitoba, Winnipeg, MB, Canada
246 rdf:type schema:Organization
247 https://www.grid.ac/institutes/grid.248762.d schema:alternateName BC Cancer Agency
248 schema:name BC Cancer Agency, 600 West 10th Avenue, V5Z 4E6, Vancouver, BC, Canada
249 Division of Medical Oncology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
250 rdf:type schema:Organization
251 https://www.grid.ac/institutes/grid.25073.33 schema:alternateName McMaster University
252 schema:name Division of Medical Oncology, Department of Oncology, McMaster University, Hamilton, ON, Canada
253 rdf:type schema:Organization
254 https://www.grid.ac/institutes/grid.270240.3 schema:alternateName Fred Hutchinson Cancer Research Center
255 schema:name Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
256 Division of Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA
257 rdf:type schema:Organization
258 https://www.grid.ac/institutes/grid.415224.4 schema:alternateName Princess Margaret Cancer Centre
259 schema:name Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia
260 Kinghorn Cancer Center, St Vincents Hospital, Sydney, NSW, Australia
261 Princess Margaret Cancer Centre, Toronto, ON, Canada
262 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...