A phase I study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors
Publication Date
June 05, 2017
Authors
Oren J. Becher, Nathan E. Millard, Shakeel Modak, Brian H. Kushner, et al
Volume
12
Issue
6
Pages
e0178593
DOI
https://dx.plos.org/10.1371/journal.pone.0178593
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0178593
Scopus
85020283031
Mendeley
http://www.mendeley.com/research/phase-i-study-singleagent-perifosine-recurrent-refractory-pediatric-cns-solid-tumors
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"A phase i study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors", "type"=>"journal", "authors"=>[{"first_name"=>"Oren J.", "last_name"=>"Becher", "scopus_author_id"=>"12806372700"}, {"first_name"=>"Nathan E.", "last_name"=>"Millard", "scopus_author_id"=>"56182056000"}, {"first_name"=>"Shakeel", "last_name"=>"Modak", "scopus_author_id"=>"7005843144"}, {"first_name"=>"Brian H.", "last_name"=>"Kushner", "scopus_author_id"=>"7103265472"}, {"first_name"=>"Sofia", "last_name"=>"Haque", "scopus_author_id"=>"55643169900"}, {"first_name"=>"Ivan", "last_name"=>"Spasojevic", "scopus_author_id"=>"57197802648"}, {"first_name"=>"Tanya M.", "last_name"=>"Trippett", "scopus_author_id"=>"6603641441"}, {"first_name"=>"Stephen W.", "last_name"=>"Gilheeney", "scopus_author_id"=>"18436537100"}, {"first_name"=>"Yasmin", "last_name"=>"Khakoo", "scopus_author_id"=>"6603130954"}, {"first_name"=>"David C.", "last_name"=>"Lyden", "scopus_author_id"=>"6602580133"}, {"first_name"=>"Kevin C.", "last_name"=>"De Braganca", "scopus_author_id"=>"24480555100"}, {"first_name"=>"Jill M.", "last_name"=>"Kolesar", "scopus_author_id"=>"7103228384"}, {"first_name"=>"Jason T.", "last_name"=>"Huse", "scopus_author_id"=>"6701377751"}, {"first_name"=>"Kim", "last_name"=>"Kramer", "scopus_author_id"=>"7201848169"}, {"first_name"=>"Nai Kong V.", "last_name"=>"Cheung", "scopus_author_id"=>"7202607914"}, {"first_name"=>"Ira J.", "last_name"=>"Dunkel", "scopus_author_id"=>"7004912949"}], "year"=>2017, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"616613901", "doi"=>"10.1371/journal.pone.0178593", "sgr"=>"85020283031", "isbn"=>"1111111111", "pmid"=>"28582410", "scopus"=>"2-s2.0-85020283031"}, "id"=>"343cdf49-b278-31d2-9199-7d12e01ae3de", "abstract"=>"The PI3K/Akt/mTOR signaling pathway is aberrantly activated in various pediatric tumors. We conducted a phase I study of the Akt inhibitor perifosine in patients with recurrent/refractory pediatric CNS and solid tumors. This was a standard 3+3 open-label dose-escalation study to assess pharmacokinetics, describe toxicities, and identify the MTD for single-agent perifosine. Five dose levels were investigated, ranging from 25 to 125 mg/m2/day for 28 days per cycle. Twenty-three patients (median age 10 years, range 4-18 years) with CNS tumors (DIPG [n = 3], high-grade glioma [n = 5], medulloblastoma [n = 2], ependymoma [n = 3]), neuroblastoma (n = 8), Wilms tumor (n = 1), and Ewing sarcoma (n = 1) were treated. Only one DLT occurred (grade 4 hyperuricemia at dose level 4). The most common grade 3 or 4 toxicity at least possibly related to perifosine was neutropenia (8.7%), with the remaining grade 3 or 4 toxicities (fatigue, hyperglycemia, fever, hyperuricemia, and catheter-related infection) occurring in one patient each. Pharmacokinetics was dose-saturable at doses above 50 mg/m2/day with significant inter-patient variability, consistent with findings reported in adult studies. One patient with DIPG (dose level 5) and 4 of 5 patients with high-grade glioma (dose levels 2 and 3) experienced stable disease for two months. Five subjects with neuroblastoma (dose levels 1 through 4) achieved stable disease which was prolonged (≥11 months) in three. No objective responses were noted. In conclusion, the use of perifosine was safe and feasible in patients with recurrent/refractory pediatric CNS and solid tumors. An MTD was not defined by the 5 dose levels investigated. Our RP2D is 50 mg/m2/day.", "link"=>"http://www.mendeley.com/research/phase-i-study-singleagent-perifosine-recurrent-refractory-pediatric-cns-solid-tumors", "reader_count"=>8, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Ph. D. Student"=>1, "Student > Postgraduate"=>1, "Other"=>2, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85020283031"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85020283031?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85020283031&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85020283031&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/85020283031", "dc:identifier"=>"SCOPUS_ID:85020283031", "eid"=>"2-s2.0-85020283031", "dc:title"=>"A phase i study of single-agent perifosine for recurrent or refractory pediatric CNS and solid tumors", "dc:creator"=>"Becher O.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"12", "prism:issueIdentifier"=>"6", "prism:pageRange"=>nil, "prism:coverDate"=>"2017-06-01", "prism:coverDisplayDate"=>"June 2017", "prism:doi"=>"10.1371/journal.pone.0178593", "citedby-count"=>"6", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Memorial Sloan-Kettering Cancer Center", "affiliation-city"=>"New York", "affiliation-country"=>"United States"}, {"@_fa"=>"true", "affilname"=>"Northwestern University", "affiliation-city"=>"Evanston", "affiliation-country"=>"United States"}], "pubmed-id"=>"28582410", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e0178593", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Counter

  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"69", "xml_views"=>"6", "html_views"=>"199"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"3", "html_views"=>"47"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"22", "xml_views"=>"2", "html_views"=>"48"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"42"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"88"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"153"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"241"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"22", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"25"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"10", "xml_views"=>"2", "html_views"=>"16"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"3", "html_views"=>"26"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"30"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"17", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"14", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"13", "xml_views"=>"3", "html_views"=>"17"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"18"}
  • {"month"=>"7", "year"=>"2019", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"8", "year"=>"2019", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"10", "year"=>"2019", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"23"}
  • {"month"=>"11", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"1", "html_views"=>"26"}

PMC Usage Stats

  • {"unique-ip"=>"23", "full-text"=>"19", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"38", "full-text"=>"42", "pdf"=>"19", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"32", "full-text"=>"31", "pdf"=>"14", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"51", "full-text"=>"51", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"39", "full-text"=>"36", "pdf"=>"17", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"31", "full-text"=>"31", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"16", "full-text"=>"18", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"22", "full-text"=>"22", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"16", "full-text"=>"15", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"16", "full-text"=>"19", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"23", "full-text"=>"30", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"18", "full-text"=>"16", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"26", "full-text"=>"27", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"26", "full-text"=>"24", "pdf"=>"10", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"16", "full-text"=>"12", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"21", "full-text"=>"29", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"16", "full-text"=>"21", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"22", "full-text"=>"19", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"6", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"12", "full-text"=>"11", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"18", "full-text"=>"19", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"26", "full-text"=>"32", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"22", "full-text"=>"30", "pdf"=>"7", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"8"}
  • {"unique-ip"=>"24", "full-text"=>"25", "pdf"=>"11", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"9"}
  • {"unique-ip"=>"18", "full-text"=>"20", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"10"}
Loading … Spinner
There are currently no alerts