A phase I study of panobinostat in pediatric patients with refractory solid tumors, including CNS tumors View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-09

AUTHORS

Paul J. Wood, Robyn Strong, Grant A. McArthur, Michael Michael, Elizabeth Algar, Andrea Muscat, Lin Rigby, Melissa Ferguson, David M. Ashley

ABSTRACT

PURPOSE: This was an open label, phase I (3 + 3 design), multi-centre study evaluating panobinostat in pediatric patients with refractory solid tumors. METHODS: Primary endpoints were to establish MTD, define and describe associated toxicities, including dose limiting toxicities (DLT) and to characterize its pharmacokinetics (PK). Secondary endpoints included assessing the anti-tumour activity of panobinostat, and its biologic activity, by measuring acetylation of histones in peripheral blood mononuclear cells. RESULTS: Nine patients were enrolled and treated with intravenous panobinostat at a dosing level of 15 mg/m2 which was tolerated. Six were evaluable for adverse events. Two (33%) patients experienced Grade 3-4 thrombocytopenia, 1 (17%) experienced Grade 3 anemia, and 2 (33%) experienced Grade 3 neutropenia. Grade 4 drug related pain occurred in 2 (33%) of the patients studied. Two (33%) patients experienced a Grade 2 QTcF change (0.478 ± 0.006 ms). One cardiac DLT (T wave changes) was reported. PK values for 15 mg/m2 (n = 9) dosing were: Tmax 0.8 h, Cmax 235.2 ng/mL, AUC0-t 346.8 h ng/mL and t1/2 7.3 h. Panobinostat significantly induced acetylation of histone H3 and H4 at all time points measured when compared to pre-treatment samples (p < 0.05). Pooled quantitative Western blot data confirmed that panobinostat significantly induced acetylation of histone H4 at 6 h (p < 0.01), 24 h (p < 0.01) and 28-70 h (p < 0.01) post dose. CONCLUSION: A significant biological effect of panobinostat, measured by acetylation status of histone H3 and H4, was achieved at a dose of 15 mg/m2. PK data and drug tolerability at 15 mg/m2 was similar to that previously published. More... »

PAGES

493-503

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-018-3634-4

DOI

http://dx.doi.org/10.1007/s00280-018-3634-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105445274

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29987369


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/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "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"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Peter MacCallum Cancer Centre", 
          "id": "https://www.grid.ac/institutes/grid.1055.1", 
          "name": [
            "Department of Paediatrics, Monash University, Melbourne, Australia", 
            "Children\u2019s Cancer Centre, Monash Children\u2019s Hospital, Melbourne, Australia", 
            "Molecular Oncology and Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wood", 
        "givenName": "Paul J.", 
        "id": "sg:person.0737711643.96", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737711643.96"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "ANZCHOG", 
          "id": "https://www.grid.ac/institutes/grid.492288.d", 
          "name": [
            "Australian & New Zealand Children\u2019s Haematology/Oncology Group (ANZCHOG), Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Strong", 
        "givenName": "Robyn", 
        "id": "sg:person.011731247030.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011731247030.03"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "St Vincent's Hospital", 
          "id": "https://www.grid.ac/institutes/grid.413105.2", 
          "name": [
            "Molecular Oncology and Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia", 
            "Department of Medicine, St. Vincent\u2019s Hospital, Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "McArthur", 
        "givenName": "Grant A.", 
        "id": "sg:person.01101164743.35", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101164743.35"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Peter MacCallum Cancer Centre", 
          "id": "https://www.grid.ac/institutes/grid.1055.1", 
          "name": [
            "Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Michael", 
        "givenName": "Michael", 
        "id": "sg:person.0673420201.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0673420201.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Hudson Institute of Medical Research", 
          "id": "https://www.grid.ac/institutes/grid.452824.d", 
          "name": [
            "Monash University, Melbourne, Australia", 
            "Hudson Institute of Medical Research, Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Algar", 
        "givenName": "Elizabeth", 
        "id": "sg:person.01313773212.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313773212.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Deakin University", 
          "id": "https://www.grid.ac/institutes/grid.1021.2", 
          "name": [
            "Deakin University, School of Medicine, Geelong, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Muscat", 
        "givenName": "Andrea", 
        "id": "sg:person.01245660012.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245660012.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Murdoch Childrens Research Institute", 
          "id": "https://www.grid.ac/institutes/grid.1058.c", 
          "name": [
            "Murdoch Children\u2019s Research Institute, Melbourne, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rigby", 
        "givenName": "Lin", 
        "id": "sg:person.01057624357.29", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01057624357.29"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Deakin University", 
          "id": "https://www.grid.ac/institutes/grid.1021.2", 
          "name": [
            "Deakin University, School of Medicine, Geelong, Australia"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ferguson", 
        "givenName": "Melissa", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Duke University Hospital", 
          "id": "https://www.grid.ac/institutes/grid.189509.c", 
          "name": [
            "The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ashley", 
        "givenName": "David M.", 
        "id": "sg:person.01222136634.47", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01222136634.47"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1200/jco.2009.25.9119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000087195"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1515/bc.1999.019", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1000562047"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.3855", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001212323", 
          "https://doi.org/10.1038/nm.3855"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1440-1746.1992.tb00982.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001250805"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-05-1225", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005915256"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s1044-579x(02)00059-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005959965"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1600-0463.2008.00957.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1007185582"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1200/jco.2006.06.4964", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010484284"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1155/2013/608964", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1011683642"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1006/excr.2000.5080", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014346356"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-2260", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017867699"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-15-2260", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017867699"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/73536", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019858955", 
          "https://doi.org/10.1038/73536"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/73536", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1019858955", 
          "https://doi.org/10.1038/73536"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.2147/ott.s30773", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1020609811"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.a.20151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021166582"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/cyto.a.20151", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021166582"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0168-9525(98)01438-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1022142141"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10637-013-9930-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023271005", 
          "https://doi.org/10.1007/s10637-013-9930-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10637-013-9930-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023271005", 
          "https://doi.org/10.1007/s10637-013-9930-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/1096-911x(20001201)35:6<577::aid-mpo18>3.0.co;2-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024041636"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1128/mcb.21.8.2726-2735.2001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029244279"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35106079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033914466", 
          "https://doi.org/10.1038/35106079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35106079", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1033914466", 
          "https://doi.org/10.1038/35106079"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s002800100300", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1035768382", 
          "https://doi.org/10.1007/s002800100300"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/hmg/10.10.1071", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1037709315"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1101/gad.217778.113", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046428161"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1158/1078-0432.ccr-06-0511", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047858383"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0960-9822(06)00042-x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049238707"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/s0960-9822(00)00114-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050674848"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/ijc.30056", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052336108"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.4161/epi.20983", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1072302530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074521031", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074680085", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074805945", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1074976760", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1076607181", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1083118277", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-09", 
    "datePublishedReg": "2018-09-01", 
    "description": "PURPOSE: This was an open label, phase I (3\u2009+\u20093 design), multi-centre study evaluating panobinostat in pediatric patients with refractory solid tumors.\nMETHODS: Primary endpoints were to establish MTD, define and describe associated toxicities, including dose limiting toxicities (DLT) and to characterize its pharmacokinetics (PK). Secondary endpoints included assessing the anti-tumour activity of panobinostat, and its biologic activity, by measuring acetylation of histones in peripheral blood mononuclear cells.\nRESULTS: Nine patients were enrolled and treated with intravenous panobinostat at a dosing level of 15\u00a0mg/m2 which was tolerated. Six were evaluable for adverse events. Two (33%) patients experienced Grade 3-4 thrombocytopenia, 1 (17%) experienced Grade 3 anemia, and 2 (33%) experienced Grade 3 neutropenia. Grade 4 drug related pain occurred in 2 (33%) of the patients studied. Two (33%) patients experienced a Grade 2\u00a0QTcF change (0.478\u2009\u00b1\u20090.006\u00a0ms). One cardiac DLT (T wave changes) was reported. PK values for 15\u00a0mg/m2 (n\u2009=\u20099) dosing were: Tmax 0.8\u00a0h, Cmax 235.2\u00a0ng/mL, AUC0-t 346.8\u00a0h\u00a0ng/mL and t1/2 7.3\u00a0h. Panobinostat significantly induced acetylation of histone H3 and H4 at all time points measured when compared to pre-treatment samples (p\u2009<\u20090.05). Pooled quantitative Western blot data confirmed that panobinostat significantly induced acetylation of histone H4 at 6 h (p\u2009<\u20090.01), 24\u00a0h (p\u2009<\u20090.01) and 28-70\u00a0h (p\u2009<\u20090.01) post dose.\nCONCLUSION: A significant biological effect of panobinostat, measured by acetylation status of histone H3 and H4, was achieved at a dose of 15\u00a0mg/m2. PK data and drug tolerability at 15\u00a0mg/m2 was similar to that previously published.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1007/s00280-018-3634-4", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": false, 
    "isPartOf": [
      {
        "id": "sg:journal.1088364", 
        "issn": [
          "0344-5704", 
          "1432-0843"
        ], 
        "name": "Cancer Chemotherapy and Pharmacology", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "3", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "82"
      }
    ], 
    "name": "A phase I study of panobinostat in pediatric patients with refractory solid tumors, including CNS tumors", 
    "pagination": "493-503", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "d517c5860d2bac2f0edc207e82d2a708857d40eaf81d70788c0b6be9dda99f31"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29987369"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "7806519"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s00280-018-3634-4"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1105445274"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s00280-018-3634-4", 
      "https://app.dimensions.ai/details/publication/pub.1105445274"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-11T11:11", 
    "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/v90/0000000353_0000000353/records_45351_00000002.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "http://link.springer.com/10.1007%2Fs00280-018-3634-4"
  }
]
 

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/s00280-018-3634-4'

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/s00280-018-3634-4'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00280-018-3634-4'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00280-018-3634-4'


 

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

245 TRIPLES      21 PREDICATES      62 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s00280-018-3634-4 schema:about anzsrc-for:11
2 anzsrc-for:1103
3 schema:author N3ca08574273449aa8c509e0b80a3033b
4 schema:citation sg:pub.10.1007/s002800100300
5 sg:pub.10.1007/s10637-013-9930-2
6 sg:pub.10.1038/35106079
7 sg:pub.10.1038/73536
8 sg:pub.10.1038/nm.3855
9 https://app.dimensions.ai/details/publication/pub.1074521031
10 https://app.dimensions.ai/details/publication/pub.1074680085
11 https://app.dimensions.ai/details/publication/pub.1074805945
12 https://app.dimensions.ai/details/publication/pub.1074976760
13 https://app.dimensions.ai/details/publication/pub.1076607181
14 https://app.dimensions.ai/details/publication/pub.1083118277
15 https://doi.org/10.1002/1096-911x(20001201)35:6<577::aid-mpo18>3.0.co;2-3
16 https://doi.org/10.1002/cyto.a.20151
17 https://doi.org/10.1002/ijc.30056
18 https://doi.org/10.1006/excr.2000.5080
19 https://doi.org/10.1016/s0168-9525(98)01438-3
20 https://doi.org/10.1016/s0960-9822(00)00114-7
21 https://doi.org/10.1016/s0960-9822(06)00042-x
22 https://doi.org/10.1016/s1044-579x(02)00059-7
23 https://doi.org/10.1093/hmg/10.10.1071
24 https://doi.org/10.1101/gad.217778.113
25 https://doi.org/10.1111/j.1440-1746.1992.tb00982.x
26 https://doi.org/10.1111/j.1600-0463.2008.00957.x
27 https://doi.org/10.1128/mcb.21.8.2726-2735.2001
28 https://doi.org/10.1155/2013/608964
29 https://doi.org/10.1158/1078-0432.ccr-05-1225
30 https://doi.org/10.1158/1078-0432.ccr-06-0511
31 https://doi.org/10.1158/1078-0432.ccr-15-2260
32 https://doi.org/10.1200/jco.2006.06.4964
33 https://doi.org/10.1200/jco.2009.25.9119
34 https://doi.org/10.1515/bc.1999.019
35 https://doi.org/10.2147/ott.s30773
36 https://doi.org/10.4161/epi.20983
37 schema:datePublished 2018-09
38 schema:datePublishedReg 2018-09-01
39 schema:description PURPOSE: This was an open label, phase I (3 + 3 design), multi-centre study evaluating panobinostat in pediatric patients with refractory solid tumors. METHODS: Primary endpoints were to establish MTD, define and describe associated toxicities, including dose limiting toxicities (DLT) and to characterize its pharmacokinetics (PK). Secondary endpoints included assessing the anti-tumour activity of panobinostat, and its biologic activity, by measuring acetylation of histones in peripheral blood mononuclear cells. RESULTS: Nine patients were enrolled and treated with intravenous panobinostat at a dosing level of 15 mg/m2 which was tolerated. Six were evaluable for adverse events. Two (33%) patients experienced Grade 3-4 thrombocytopenia, 1 (17%) experienced Grade 3 anemia, and 2 (33%) experienced Grade 3 neutropenia. Grade 4 drug related pain occurred in 2 (33%) of the patients studied. Two (33%) patients experienced a Grade 2 QTcF change (0.478 ± 0.006 ms). One cardiac DLT (T wave changes) was reported. PK values for 15 mg/m2 (n = 9) dosing were: Tmax 0.8 h, Cmax 235.2 ng/mL, AUC0-t 346.8 h ng/mL and t1/2 7.3 h. Panobinostat significantly induced acetylation of histone H3 and H4 at all time points measured when compared to pre-treatment samples (p < 0.05). Pooled quantitative Western blot data confirmed that panobinostat significantly induced acetylation of histone H4 at 6 h (p < 0.01), 24 h (p < 0.01) and 28-70 h (p < 0.01) post dose. CONCLUSION: A significant biological effect of panobinostat, measured by acetylation status of histone H3 and H4, was achieved at a dose of 15 mg/m2. PK data and drug tolerability at 15 mg/m2 was similar to that previously published.
40 schema:genre research_article
41 schema:inLanguage en
42 schema:isAccessibleForFree false
43 schema:isPartOf N52c48cffc8a84e5d97e8e80cd320c626
44 Na4aa9521e0ef4c04a36dfbfc0dd6b445
45 sg:journal.1088364
46 schema:name A phase I study of panobinostat in pediatric patients with refractory solid tumors, including CNS tumors
47 schema:pagination 493-503
48 schema:productId N2cd072c0bdc14b3db5618ac20928eba7
49 N8549883fb10e4d42b9c5e92e9ea1bee1
50 Nadfe8fddfb374c3e8e714e57c71d70f3
51 Nd1ba4af2eae34caa9e249c2cedc361fd
52 Necaa24187a0c40e2b7afd5fea7f15a92
53 schema:sameAs https://app.dimensions.ai/details/publication/pub.1105445274
54 https://doi.org/10.1007/s00280-018-3634-4
55 schema:sdDatePublished 2019-04-11T11:11
56 schema:sdLicense https://scigraph.springernature.com/explorer/license/
57 schema:sdPublisher N97dfdf51c41042d3b171f03d73dab019
58 schema:url http://link.springer.com/10.1007%2Fs00280-018-3634-4
59 sgo:license sg:explorer/license/
60 sgo:sdDataset articles
61 rdf:type schema:ScholarlyArticle
62 N2c3af64c874e453895897cc51c9057ee schema:affiliation https://www.grid.ac/institutes/grid.1021.2
63 schema:familyName Ferguson
64 schema:givenName Melissa
65 rdf:type schema:Person
66 N2cd072c0bdc14b3db5618ac20928eba7 schema:name doi
67 schema:value 10.1007/s00280-018-3634-4
68 rdf:type schema:PropertyValue
69 N3ca08574273449aa8c509e0b80a3033b rdf:first sg:person.0737711643.96
70 rdf:rest N83c79aa85bfe4d0a9457d4f0c49e1cdb
71 N475dbe5207dc40a08df6e619579ec44b rdf:first sg:person.01057624357.29
72 rdf:rest Nc033d15d12344322a6bd47bdc3a46a8b
73 N52c48cffc8a84e5d97e8e80cd320c626 schema:volumeNumber 82
74 rdf:type schema:PublicationVolume
75 N60344f8939ee4abeb3ca3bd4580c5e40 rdf:first sg:person.01222136634.47
76 rdf:rest rdf:nil
77 N83c79aa85bfe4d0a9457d4f0c49e1cdb rdf:first sg:person.011731247030.03
78 rdf:rest N9f3b80174f62461f9689012a412b8449
79 N8549883fb10e4d42b9c5e92e9ea1bee1 schema:name nlm_unique_id
80 schema:value 7806519
81 rdf:type schema:PropertyValue
82 N97955e56b338459caf4a0a97f7360d0d rdf:first sg:person.0673420201.89
83 rdf:rest Na997adf5d5064b49bb9726058769fcc7
84 N97dfdf51c41042d3b171f03d73dab019 schema:name Springer Nature - SN SciGraph project
85 rdf:type schema:Organization
86 N9f3b80174f62461f9689012a412b8449 rdf:first sg:person.01101164743.35
87 rdf:rest N97955e56b338459caf4a0a97f7360d0d
88 Na4aa9521e0ef4c04a36dfbfc0dd6b445 schema:issueNumber 3
89 rdf:type schema:PublicationIssue
90 Na997adf5d5064b49bb9726058769fcc7 rdf:first sg:person.01313773212.37
91 rdf:rest Nff416d2b79584da3961d7ef1b080a0ee
92 Nadfe8fddfb374c3e8e714e57c71d70f3 schema:name dimensions_id
93 schema:value pub.1105445274
94 rdf:type schema:PropertyValue
95 Nc033d15d12344322a6bd47bdc3a46a8b rdf:first N2c3af64c874e453895897cc51c9057ee
96 rdf:rest N60344f8939ee4abeb3ca3bd4580c5e40
97 Nd1ba4af2eae34caa9e249c2cedc361fd schema:name readcube_id
98 schema:value d517c5860d2bac2f0edc207e82d2a708857d40eaf81d70788c0b6be9dda99f31
99 rdf:type schema:PropertyValue
100 Necaa24187a0c40e2b7afd5fea7f15a92 schema:name pubmed_id
101 schema:value 29987369
102 rdf:type schema:PropertyValue
103 Nff416d2b79584da3961d7ef1b080a0ee rdf:first sg:person.01245660012.49
104 rdf:rest N475dbe5207dc40a08df6e619579ec44b
105 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
106 schema:name Medical and Health Sciences
107 rdf:type schema:DefinedTerm
108 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
109 schema:name Clinical Sciences
110 rdf:type schema:DefinedTerm
111 sg:journal.1088364 schema:issn 0344-5704
112 1432-0843
113 schema:name Cancer Chemotherapy and Pharmacology
114 rdf:type schema:Periodical
115 sg:person.01057624357.29 schema:affiliation https://www.grid.ac/institutes/grid.1058.c
116 schema:familyName Rigby
117 schema:givenName Lin
118 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01057624357.29
119 rdf:type schema:Person
120 sg:person.01101164743.35 schema:affiliation https://www.grid.ac/institutes/grid.413105.2
121 schema:familyName McArthur
122 schema:givenName Grant A.
123 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01101164743.35
124 rdf:type schema:Person
125 sg:person.011731247030.03 schema:affiliation https://www.grid.ac/institutes/grid.492288.d
126 schema:familyName Strong
127 schema:givenName Robyn
128 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011731247030.03
129 rdf:type schema:Person
130 sg:person.01222136634.47 schema:affiliation https://www.grid.ac/institutes/grid.189509.c
131 schema:familyName Ashley
132 schema:givenName David M.
133 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01222136634.47
134 rdf:type schema:Person
135 sg:person.01245660012.49 schema:affiliation https://www.grid.ac/institutes/grid.1021.2
136 schema:familyName Muscat
137 schema:givenName Andrea
138 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01245660012.49
139 rdf:type schema:Person
140 sg:person.01313773212.37 schema:affiliation https://www.grid.ac/institutes/grid.452824.d
141 schema:familyName Algar
142 schema:givenName Elizabeth
143 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01313773212.37
144 rdf:type schema:Person
145 sg:person.0673420201.89 schema:affiliation https://www.grid.ac/institutes/grid.1055.1
146 schema:familyName Michael
147 schema:givenName Michael
148 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0673420201.89
149 rdf:type schema:Person
150 sg:person.0737711643.96 schema:affiliation https://www.grid.ac/institutes/grid.1055.1
151 schema:familyName Wood
152 schema:givenName Paul J.
153 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0737711643.96
154 rdf:type schema:Person
155 sg:pub.10.1007/s002800100300 schema:sameAs https://app.dimensions.ai/details/publication/pub.1035768382
156 https://doi.org/10.1007/s002800100300
157 rdf:type schema:CreativeWork
158 sg:pub.10.1007/s10637-013-9930-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023271005
159 https://doi.org/10.1007/s10637-013-9930-2
160 rdf:type schema:CreativeWork
161 sg:pub.10.1038/35106079 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033914466
162 https://doi.org/10.1038/35106079
163 rdf:type schema:CreativeWork
164 sg:pub.10.1038/73536 schema:sameAs https://app.dimensions.ai/details/publication/pub.1019858955
165 https://doi.org/10.1038/73536
166 rdf:type schema:CreativeWork
167 sg:pub.10.1038/nm.3855 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001212323
168 https://doi.org/10.1038/nm.3855
169 rdf:type schema:CreativeWork
170 https://app.dimensions.ai/details/publication/pub.1074521031 schema:CreativeWork
171 https://app.dimensions.ai/details/publication/pub.1074680085 schema:CreativeWork
172 https://app.dimensions.ai/details/publication/pub.1074805945 schema:CreativeWork
173 https://app.dimensions.ai/details/publication/pub.1074976760 schema:CreativeWork
174 https://app.dimensions.ai/details/publication/pub.1076607181 schema:CreativeWork
175 https://app.dimensions.ai/details/publication/pub.1083118277 schema:CreativeWork
176 https://doi.org/10.1002/1096-911x(20001201)35:6<577::aid-mpo18>3.0.co;2-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024041636
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1002/cyto.a.20151 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021166582
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1002/ijc.30056 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052336108
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1006/excr.2000.5080 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014346356
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1016/s0168-9525(98)01438-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1022142141
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1016/s0960-9822(00)00114-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050674848
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1016/s0960-9822(06)00042-x schema:sameAs https://app.dimensions.ai/details/publication/pub.1049238707
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1016/s1044-579x(02)00059-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005959965
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1093/hmg/10.10.1071 schema:sameAs https://app.dimensions.ai/details/publication/pub.1037709315
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1101/gad.217778.113 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046428161
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1111/j.1440-1746.1992.tb00982.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1001250805
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1111/j.1600-0463.2008.00957.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1007185582
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1128/mcb.21.8.2726-2735.2001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029244279
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1155/2013/608964 schema:sameAs https://app.dimensions.ai/details/publication/pub.1011683642
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1158/1078-0432.ccr-05-1225 schema:sameAs https://app.dimensions.ai/details/publication/pub.1005915256
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1158/1078-0432.ccr-06-0511 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047858383
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1158/1078-0432.ccr-15-2260 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017867699
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1200/jco.2006.06.4964 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010484284
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1200/jco.2009.25.9119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000087195
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1515/bc.1999.019 schema:sameAs https://app.dimensions.ai/details/publication/pub.1000562047
215 rdf:type schema:CreativeWork
216 https://doi.org/10.2147/ott.s30773 schema:sameAs https://app.dimensions.ai/details/publication/pub.1020609811
217 rdf:type schema:CreativeWork
218 https://doi.org/10.4161/epi.20983 schema:sameAs https://app.dimensions.ai/details/publication/pub.1072302530
219 rdf:type schema:CreativeWork
220 https://www.grid.ac/institutes/grid.1021.2 schema:alternateName Deakin University
221 schema:name Deakin University, School of Medicine, Geelong, Australia
222 rdf:type schema:Organization
223 https://www.grid.ac/institutes/grid.1055.1 schema:alternateName Peter MacCallum Cancer Centre
224 schema:name Children’s Cancer Centre, Monash Children’s Hospital, Melbourne, Australia
225 Department of Paediatrics, Monash University, Melbourne, Australia
226 Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia
227 Molecular Oncology and Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
228 rdf:type schema:Organization
229 https://www.grid.ac/institutes/grid.1058.c schema:alternateName Murdoch Childrens Research Institute
230 schema:name Murdoch Children’s Research Institute, Melbourne, Australia
231 rdf:type schema:Organization
232 https://www.grid.ac/institutes/grid.189509.c schema:alternateName Duke University Hospital
233 schema:name The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA
234 rdf:type schema:Organization
235 https://www.grid.ac/institutes/grid.413105.2 schema:alternateName St Vincent's Hospital
236 schema:name Department of Medicine, St. Vincent’s Hospital, Melbourne, Australia
237 Molecular Oncology and Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Australia
238 rdf:type schema:Organization
239 https://www.grid.ac/institutes/grid.452824.d schema:alternateName Hudson Institute of Medical Research
240 schema:name Hudson Institute of Medical Research, Melbourne, Australia
241 Monash University, Melbourne, Australia
242 rdf:type schema:Organization
243 https://www.grid.ac/institutes/grid.492288.d schema:alternateName ANZCHOG
244 schema:name Australian & New Zealand Children’s Haematology/Oncology Group (ANZCHOG), Melbourne, Australia
245 rdf:type schema:Organization
 




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


...