Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2015-09-11

AUTHORS

Robert J. Morgan, Timothy W. Synold, Jeffrey A. Longmate, David I. Quinn, David Gandara, Heinz-Josef Lenz, Christopher Ruel, Bixin Xi, Michael D. Lewis, A. Dimitrios Colevas, James Doroshow, Edward M. Newman

ABSTRACT

Background The California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3 weeks out of four.MethodsThis trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single-patient cohorts were enrolled with intra- and inter-patient dose doubling. The second phase was a standard 3 + 3 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125 mg/m2, and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay.ResultsForty patients were entered. Thirty-eight were evaluable for toxicity and 35 for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5 mg/m2/week. The second phase ended at 2.0 mg/m2/week with dose-limiting toxicities of grades 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m2/week. Responses included four partial responses (lung cancer [2], urothelial [1], and melanoma [1]).ConclusionsE7389 was well tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of β-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveal that E7389 exhibits a tri-exponential elimination from the plasma of patients receiving a rapid i.v. infusion. At sub-toxic doses, plasma concentrations of E7389 are maintained well above the levels required for activity in vitro for >72 h. More... »

PAGES

897-907

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-015-2868-7

DOI

http://dx.doi.org/10.1007/s00280-015-2868-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028528026

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26362045


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/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "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"
      }, 
      {
        "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": "Antineoplastic Agents", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Breast Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Dose-Response Relationship, Drug", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Drug Monitoring", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Febrile Neutropenia", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Furans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Injections, Intravenous", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Ketones", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lymphopenia", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Male", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Melanoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Ovarian Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Salvage Therapy", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tubulin Modulators", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Urologic Neoplasms", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Morgan", 
        "givenName": "Robert J.", 
        "id": "sg:person.012661132562.89", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012661132562.89"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Synold", 
        "givenName": "Timothy W.", 
        "id": "sg:person.010054353347.22", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010054353347.22"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Longmate", 
        "givenName": "Jeffrey A.", 
        "id": "sg:person.016211117070.31", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016211117070.31"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.42505.36", 
          "name": [
            "Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Quinn", 
        "givenName": "David I.", 
        "id": "sg:person.01013134010.15", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013134010.15"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Medical Oncology, University of California, Davis Cancer Center, Sacramento, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.27860.3b", 
          "name": [
            "Division of Medical Oncology, University of California, Davis Cancer Center, Sacramento, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Gandara", 
        "givenName": "David", 
        "id": "sg:person.0644235622.37", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644235622.37"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.42505.36", 
          "name": [
            "Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lenz", 
        "givenName": "Heinz-Josef", 
        "id": "sg:person.0732636217.43", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732636217.43"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ruel", 
        "givenName": "Christopher", 
        "id": "sg:person.0723206057.57", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723206057.57"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Xi", 
        "givenName": "Bixin", 
        "id": "sg:person.01160474102.34", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160474102.34"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Edward P. Evans Foundation, 20139, Casanova, VA, USA", 
          "id": "http://www.grid.ac/institutes/grid.478860.5", 
          "name": [
            "Eisai Research Institute, 01810, Andover, MA, USA", 
            "Edward P. Evans Foundation, 20139, Casanova, VA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Lewis", 
        "givenName": "Michael D.", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Stanford Cancer Center, 94305, Stanford, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.168010.e", 
          "name": [
            "Division of Cancer Treatment and Diagnosis, National Cancer Institute, 20892, Bethesda, MD, USA", 
            "Stanford Cancer Center, 94305, Stanford, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Colevas", 
        "givenName": "A. Dimitrios", 
        "id": "sg:person.07523621747.49", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07523621747.49"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Division of Cancer Treatment and Diagnosis6, National Cancer Institute, 20892, Bethesda, MD, USA", 
          "id": "http://www.grid.ac/institutes/grid.48336.3a", 
          "name": [
            "Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA", 
            "Division of Cancer Treatment and Diagnosis6, National Cancer Institute, 20892, Bethesda, MD, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Doroshow", 
        "givenName": "James", 
        "id": "sg:person.01135535666.03", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01135535666.03"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA", 
          "id": "http://www.grid.ac/institutes/grid.410425.6", 
          "name": [
            "Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Newman", 
        "givenName": "Edward M.", 
        "id": "sg:person.01346143476.85", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346143476.85"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.onc.1203642", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1034107285", 
          "https://doi.org/10.1038/sj.onc.1203642"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nchembio840", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050584708", 
          "https://doi.org/10.1038/nchembio840"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2015-09-11", 
    "datePublishedReg": "2015-09-11", 
    "description": "Background\nThe California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3\u00a0weeks out of four.MethodsThis trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single-patient cohorts were enrolled with intra- and inter-patient dose doubling. The second phase was a standard 3\u00a0+\u00a03 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125\u00a0mg/m2, and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay.ResultsForty patients were entered. Thirty-eight were evaluable for toxicity and 35 for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5\u00a0mg/m2/week. The second phase ended at 2.0\u00a0mg/m2/week with dose-limiting toxicities of grades 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4\u00a0mg/m2/week. Responses included four partial responses (lung cancer [2], urothelial [1], and melanoma [1]).ConclusionsE7389 was well tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of \u03b2-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveal that E7389 exhibits a tri-exponential elimination from the plasma of patients receiving a rapid i.v. infusion. At sub-toxic doses, plasma concentrations of E7389 are maintained well above the levels required for activity in vitro for >72\u00a0h.", 
    "genre": "article", 
    "id": "sg:pub.10.1007/s00280-015-2868-7", 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2423964", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2688666", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2438805", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2724037", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.2438845", 
        "type": "MonetaryGrant"
      }, 
      {
        "id": "sg:grant.3535689", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1088364", 
        "issn": [
          "0344-5704", 
          "1432-0843"
        ], 
        "name": "Cancer Chemotherapy and Pharmacology", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "5", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "76"
      }
    ], 
    "keywords": [
      "intra-tumoral levels", 
      "phase I trial", 
      "I trial", 
      "California Cancer Consortium Trial", 
      "peripheral blood mononuclear cells", 
      "California Cancer Consortium", 
      "single-patient cohorts", 
      "dose escalation schedule", 
      "grade 3 elevation", 
      "advanced solid tumors", 
      "cohort of patients", 
      "dose-limiting toxicity", 
      "blood mononuclear cells", 
      "plasma of patients", 
      "\u03b2-tubulin III", 
      "LC/MS/MS assay", 
      "significant morphologic changes", 
      "sub-toxic doses", 
      "injection weekly", 
      "MethodsThis trial", 
      "dose doubling", 
      "escalation schedule", 
      "ResultsForty patients", 
      "febrile neutropenia", 
      "real-time pharmacokinetics", 
      "starting dose", 
      "partial response", 
      "major toxicity", 
      "Consortium Trial", 
      "dose escalation", 
      "mononuclear cells", 
      "plasma concentrations", 
      "grade 3", 
      "titration design", 
      "urine sampling", 
      "patients", 
      "PK data", 
      "solid tumors", 
      "Cancer Consortium", 
      "doses 1", 
      "MS/MS assay", 
      "pharmacodynamics", 
      "pharmacokinetics", 
      "target validation studies", 
      "morphologic changes", 
      "tumor cells", 
      "trials", 
      "weeks", 
      "MTD", 
      "cycle 1", 
      "cohort", 
      "alkaline phosphatase", 
      "doses", 
      "toxicity", 
      "MS assay", 
      "validation study", 
      "rapid escalation", 
      "escalation", 
      "response", 
      "neutropenia", 
      "myelosuppression", 
      "hypophosphatemia", 
      "cells", 
      "hypoglycemia", 
      "levels", 
      "tumors", 
      "dose", 
      "blood", 
      "progression", 
      "weekly", 
      "halichondrin B.", 
      "vivo", 
      "elevation", 
      "assays", 
      "stathmin", 
      "second phase", 
      "B.", 
      "fatigue", 
      "MAP4", 
      "phosphatase", 
      "data", 
      "intra", 
      "schedule", 
      "plasma", 
      "E7389", 
      "activity", 
      "elimination", 
      "study", 
      "first phase", 
      "background", 
      "m2", 
      "changes", 
      "concentration", 
      "microtubules", 
      "analogues", 
      "doubling", 
      "consortium", 
      "sampling", 
      "phase", 
      "design"
    ], 
    "name": "Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer Consortium trial", 
    "pagination": "897-907", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1028528026"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1007/s00280-015-2868-7"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "26362045"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1007/s00280-015-2868-7", 
      "https://app.dimensions.ai/details/publication/pub.1028528026"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-09-02T15:59", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_681.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1007/s00280-015-2868-7"
  }
]
 

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/s00280-015-2868-7'

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/s00280-015-2868-7'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00280-015-2868-7'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00280-015-2868-7'


 

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

371 TRIPLES      21 PREDICATES      150 URIs      140 LITERALS      30 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1007/s00280-015-2868-7 schema:about N294b3a7347554cf39d8b8af585b49fc6
2 N2fa4c1c43c2a4a80b6d95fe8cbc129c6
3 N4426c2d08b814f948b6e463b759c1969
4 N44f30d6c845e4564876ebb96d63eceb2
5 N4a6cac7e952f4b06b030e5ba1cb1c6b1
6 N681ed88bbcae42e4b876d27dce8ff34f
7 N68c7b81a2fd949749f60392b6eb6e0e8
8 N6bf3965363e348cf926aac8991d16488
9 N73041a636b9a428a99fe06b903a4e6ff
10 N83f2b3bf8a954f2aa2fe5d344d6dd4d8
11 N8aaf29bf717f427baf7351c707ec9373
12 N9092c04646d54a8d856bf88db37d7e73
13 N911221d0f2974769a10d9265b68b3b46
14 N9681b3e39aee4a33b572cec402679b8e
15 Na4af3a8168c845a0b05caf5e33e4e911
16 Nb36fb28f0c304f8f81840a714947a0a2
17 Nbedc43d581fc47639b82f806e722c15e
18 Nc0dcc603f2a94c4da493533a0c9c53e2
19 Ndde152e78e2e4ae5984a32e63464294b
20 Ne6b3757e35e94840beafa0f5396959cb
21 Nf4722dcd18f5471db4afb57df4b3b59b
22 Nf73629d8cc784cfea1b460d4669ade22
23 Nff15b7231f414d92982cb16cf0e9cfec
24 anzsrc-for:11
25 anzsrc-for:1112
26 schema:author N414296829647411596b0fea78c898181
27 schema:citation sg:pub.10.1038/nchembio840
28 sg:pub.10.1038/sj.onc.1203642
29 schema:datePublished 2015-09-11
30 schema:datePublishedReg 2015-09-11
31 schema:description Background The California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3 weeks out of four.MethodsThis trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single-patient cohorts were enrolled with intra- and inter-patient dose doubling. The second phase was a standard 3 + 3 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125 mg/m2, and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay.ResultsForty patients were entered. Thirty-eight were evaluable for toxicity and 35 for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5 mg/m2/week. The second phase ended at 2.0 mg/m2/week with dose-limiting toxicities of grades 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m2/week. Responses included four partial responses (lung cancer [2], urothelial [1], and melanoma [1]).ConclusionsE7389 was well tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of β-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveal that E7389 exhibits a tri-exponential elimination from the plasma of patients receiving a rapid i.v. infusion. At sub-toxic doses, plasma concentrations of E7389 are maintained well above the levels required for activity in vitro for >72 h.
32 schema:genre article
33 schema:isAccessibleForFree true
34 schema:isPartOf N7d1d024fc0184c7c96143bd8a4a5d379
35 Nb6f8d27666af46989b97306dc2212805
36 sg:journal.1088364
37 schema:keywords B.
38 California Cancer Consortium
39 California Cancer Consortium Trial
40 Cancer Consortium
41 Consortium Trial
42 E7389
43 I trial
44 LC/MS/MS assay
45 MAP4
46 MS assay
47 MS/MS assay
48 MTD
49 MethodsThis trial
50 PK data
51 ResultsForty patients
52 activity
53 advanced solid tumors
54 alkaline phosphatase
55 analogues
56 assays
57 background
58 blood
59 blood mononuclear cells
60 cells
61 changes
62 cohort
63 cohort of patients
64 concentration
65 consortium
66 cycle 1
67 data
68 design
69 dose
70 dose doubling
71 dose escalation
72 dose escalation schedule
73 dose-limiting toxicity
74 doses
75 doses 1
76 doubling
77 elevation
78 elimination
79 escalation
80 escalation schedule
81 fatigue
82 febrile neutropenia
83 first phase
84 grade 3
85 grade 3 elevation
86 halichondrin B.
87 hypoglycemia
88 hypophosphatemia
89 injection weekly
90 intra
91 intra-tumoral levels
92 levels
93 m2
94 major toxicity
95 microtubules
96 mononuclear cells
97 morphologic changes
98 myelosuppression
99 neutropenia
100 partial response
101 patients
102 peripheral blood mononuclear cells
103 pharmacodynamics
104 pharmacokinetics
105 phase
106 phase I trial
107 phosphatase
108 plasma
109 plasma concentrations
110 plasma of patients
111 progression
112 rapid escalation
113 real-time pharmacokinetics
114 response
115 sampling
116 schedule
117 second phase
118 significant morphologic changes
119 single-patient cohorts
120 solid tumors
121 starting dose
122 stathmin
123 study
124 sub-toxic doses
125 target validation studies
126 titration design
127 toxicity
128 trials
129 tumor cells
130 tumors
131 urine sampling
132 validation study
133 vivo
134 weekly
135 weeks
136 β-tubulin III
137 schema:name Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin, halichondrin B analog) during a phase I trial in patients with advanced solid tumors: a California Cancer Consortium trial
138 schema:pagination 897-907
139 schema:productId N821cbef7bb154ddbacc3cabcc0d96c4b
140 Nbded2b5d244241978ab04d72394c4f3c
141 Nbebf02db01f74961930b27c522c6b068
142 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028528026
143 https://doi.org/10.1007/s00280-015-2868-7
144 schema:sdDatePublished 2022-09-02T15:59
145 schema:sdLicense https://scigraph.springernature.com/explorer/license/
146 schema:sdPublisher Nb42d6cb1038d440e8cb5cacca21a479e
147 schema:url https://doi.org/10.1007/s00280-015-2868-7
148 sgo:license sg:explorer/license/
149 sgo:sdDataset articles
150 rdf:type schema:ScholarlyArticle
151 N053a8d825f68424fad82bac405c619cd rdf:first sg:person.0644235622.37
152 rdf:rest N1428f33dc79b42729771f82c8e978553
153 N1428f33dc79b42729771f82c8e978553 rdf:first sg:person.0732636217.43
154 rdf:rest Na6b1add0dca84520b631004ccc5a889a
155 N294b3a7347554cf39d8b8af585b49fc6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
156 schema:name Humans
157 rdf:type schema:DefinedTerm
158 N2fa4c1c43c2a4a80b6d95fe8cbc129c6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
159 schema:name Salvage Therapy
160 rdf:type schema:DefinedTerm
161 N35d4b205e5194b06bca690bf550d164a rdf:first sg:person.07523621747.49
162 rdf:rest N449a4ffa499241e7b673be03490a7785
163 N414296829647411596b0fea78c898181 rdf:first sg:person.012661132562.89
164 rdf:rest Na3d1104efd3a4fb58a7d1a1f9f7ded3f
165 N4426c2d08b814f948b6e463b759c1969 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
166 schema:name Ketones
167 rdf:type schema:DefinedTerm
168 N449a4ffa499241e7b673be03490a7785 rdf:first sg:person.01135535666.03
169 rdf:rest Nc655e00271cc42bb8a1361d132034577
170 N44f30d6c845e4564876ebb96d63eceb2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Female
172 rdf:type schema:DefinedTerm
173 N4a6cac7e952f4b06b030e5ba1cb1c6b1 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name Middle Aged
175 rdf:type schema:DefinedTerm
176 N4be1013e597b4dc6b0122a8f67058754 rdf:first sg:person.01160474102.34
177 rdf:rest N57cf9726d188439fab82d7ee22978d98
178 N57cf9726d188439fab82d7ee22978d98 rdf:first N5c6fc39e73604ef58773bbf531ede991
179 rdf:rest N35d4b205e5194b06bca690bf550d164a
180 N5c6fc39e73604ef58773bbf531ede991 schema:affiliation grid-institutes:grid.478860.5
181 schema:familyName Lewis
182 schema:givenName Michael D.
183 rdf:type schema:Person
184 N681ed88bbcae42e4b876d27dce8ff34f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
185 schema:name Furans
186 rdf:type schema:DefinedTerm
187 N68c7b81a2fd949749f60392b6eb6e0e8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
188 schema:name Adult
189 rdf:type schema:DefinedTerm
190 N6bf3965363e348cf926aac8991d16488 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
191 schema:name Aged, 80 and over
192 rdf:type schema:DefinedTerm
193 N73041a636b9a428a99fe06b903a4e6ff schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
194 schema:name Injections, Intravenous
195 rdf:type schema:DefinedTerm
196 N7d1d024fc0184c7c96143bd8a4a5d379 schema:volumeNumber 76
197 rdf:type schema:PublicationVolume
198 N821cbef7bb154ddbacc3cabcc0d96c4b schema:name dimensions_id
199 schema:value pub.1028528026
200 rdf:type schema:PropertyValue
201 N83f2b3bf8a954f2aa2fe5d344d6dd4d8 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
202 schema:name Lymphopenia
203 rdf:type schema:DefinedTerm
204 N8761d6cfe1a041c8b9281d97f54bd055 rdf:first sg:person.01013134010.15
205 rdf:rest N053a8d825f68424fad82bac405c619cd
206 N8aaf29bf717f427baf7351c707ec9373 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
207 schema:name Male
208 rdf:type schema:DefinedTerm
209 N9092c04646d54a8d856bf88db37d7e73 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
210 schema:name Tubulin Modulators
211 rdf:type schema:DefinedTerm
212 N911221d0f2974769a10d9265b68b3b46 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
213 schema:name Aged
214 rdf:type schema:DefinedTerm
215 N9681b3e39aee4a33b572cec402679b8e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
216 schema:name Melanoma
217 rdf:type schema:DefinedTerm
218 Na3d1104efd3a4fb58a7d1a1f9f7ded3f rdf:first sg:person.010054353347.22
219 rdf:rest Ncef165ba1dc74450b601ffaede90e32e
220 Na4af3a8168c845a0b05caf5e33e4e911 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
221 schema:name Urologic Neoplasms
222 rdf:type schema:DefinedTerm
223 Na6b1add0dca84520b631004ccc5a889a rdf:first sg:person.0723206057.57
224 rdf:rest N4be1013e597b4dc6b0122a8f67058754
225 Nb36fb28f0c304f8f81840a714947a0a2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
226 schema:name Drug Monitoring
227 rdf:type schema:DefinedTerm
228 Nb42d6cb1038d440e8cb5cacca21a479e schema:name Springer Nature - SN SciGraph project
229 rdf:type schema:Organization
230 Nb6f8d27666af46989b97306dc2212805 schema:issueNumber 5
231 rdf:type schema:PublicationIssue
232 Nbded2b5d244241978ab04d72394c4f3c schema:name doi
233 schema:value 10.1007/s00280-015-2868-7
234 rdf:type schema:PropertyValue
235 Nbebf02db01f74961930b27c522c6b068 schema:name pubmed_id
236 schema:value 26362045
237 rdf:type schema:PropertyValue
238 Nbedc43d581fc47639b82f806e722c15e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
239 schema:name Breast Neoplasms
240 rdf:type schema:DefinedTerm
241 Nc0dcc603f2a94c4da493533a0c9c53e2 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
242 schema:name Ovarian Neoplasms
243 rdf:type schema:DefinedTerm
244 Nc655e00271cc42bb8a1361d132034577 rdf:first sg:person.01346143476.85
245 rdf:rest rdf:nil
246 Ncef165ba1dc74450b601ffaede90e32e rdf:first sg:person.016211117070.31
247 rdf:rest N8761d6cfe1a041c8b9281d97f54bd055
248 Ndde152e78e2e4ae5984a32e63464294b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
249 schema:name Febrile Neutropenia
250 rdf:type schema:DefinedTerm
251 Ne6b3757e35e94840beafa0f5396959cb schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
252 schema:name Lung Neoplasms
253 rdf:type schema:DefinedTerm
254 Nf4722dcd18f5471db4afb57df4b3b59b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
255 schema:name Dose-Response Relationship, Drug
256 rdf:type schema:DefinedTerm
257 Nf73629d8cc784cfea1b460d4669ade22 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
258 schema:name Carcinoma
259 rdf:type schema:DefinedTerm
260 Nff15b7231f414d92982cb16cf0e9cfec schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
261 schema:name Antineoplastic Agents
262 rdf:type schema:DefinedTerm
263 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
264 schema:name Medical and Health Sciences
265 rdf:type schema:DefinedTerm
266 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
267 schema:name Oncology and Carcinogenesis
268 rdf:type schema:DefinedTerm
269 sg:grant.2423964 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
270 rdf:type schema:MonetaryGrant
271 sg:grant.2438805 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
272 rdf:type schema:MonetaryGrant
273 sg:grant.2438845 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
274 rdf:type schema:MonetaryGrant
275 sg:grant.2688666 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
276 rdf:type schema:MonetaryGrant
277 sg:grant.2724037 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
278 rdf:type schema:MonetaryGrant
279 sg:grant.3535689 http://pending.schema.org/fundedItem sg:pub.10.1007/s00280-015-2868-7
280 rdf:type schema:MonetaryGrant
281 sg:journal.1088364 schema:issn 0344-5704
282 1432-0843
283 schema:name Cancer Chemotherapy and Pharmacology
284 schema:publisher Springer Nature
285 rdf:type schema:Periodical
286 sg:person.010054353347.22 schema:affiliation grid-institutes:grid.410425.6
287 schema:familyName Synold
288 schema:givenName Timothy W.
289 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.010054353347.22
290 rdf:type schema:Person
291 sg:person.01013134010.15 schema:affiliation grid-institutes:grid.42505.36
292 schema:familyName Quinn
293 schema:givenName David I.
294 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01013134010.15
295 rdf:type schema:Person
296 sg:person.01135535666.03 schema:affiliation grid-institutes:grid.48336.3a
297 schema:familyName Doroshow
298 schema:givenName James
299 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01135535666.03
300 rdf:type schema:Person
301 sg:person.01160474102.34 schema:affiliation grid-institutes:grid.410425.6
302 schema:familyName Xi
303 schema:givenName Bixin
304 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01160474102.34
305 rdf:type schema:Person
306 sg:person.012661132562.89 schema:affiliation grid-institutes:grid.410425.6
307 schema:familyName Morgan
308 schema:givenName Robert J.
309 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012661132562.89
310 rdf:type schema:Person
311 sg:person.01346143476.85 schema:affiliation grid-institutes:grid.410425.6
312 schema:familyName Newman
313 schema:givenName Edward M.
314 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346143476.85
315 rdf:type schema:Person
316 sg:person.016211117070.31 schema:affiliation grid-institutes:grid.410425.6
317 schema:familyName Longmate
318 schema:givenName Jeffrey A.
319 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.016211117070.31
320 rdf:type schema:Person
321 sg:person.0644235622.37 schema:affiliation grid-institutes:grid.27860.3b
322 schema:familyName Gandara
323 schema:givenName David
324 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0644235622.37
325 rdf:type schema:Person
326 sg:person.0723206057.57 schema:affiliation grid-institutes:grid.410425.6
327 schema:familyName Ruel
328 schema:givenName Christopher
329 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0723206057.57
330 rdf:type schema:Person
331 sg:person.0732636217.43 schema:affiliation grid-institutes:grid.42505.36
332 schema:familyName Lenz
333 schema:givenName Heinz-Josef
334 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732636217.43
335 rdf:type schema:Person
336 sg:person.07523621747.49 schema:affiliation grid-institutes:grid.168010.e
337 schema:familyName Colevas
338 schema:givenName A. Dimitrios
339 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07523621747.49
340 rdf:type schema:Person
341 sg:pub.10.1038/nchembio840 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050584708
342 https://doi.org/10.1038/nchembio840
343 rdf:type schema:CreativeWork
344 sg:pub.10.1038/sj.onc.1203642 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034107285
345 https://doi.org/10.1038/sj.onc.1203642
346 rdf:type schema:CreativeWork
347 grid-institutes:grid.168010.e schema:alternateName Stanford Cancer Center, 94305, Stanford, CA, USA
348 schema:name Division of Cancer Treatment and Diagnosis, National Cancer Institute, 20892, Bethesda, MD, USA
349 Stanford Cancer Center, 94305, Stanford, CA, USA
350 rdf:type schema:Organization
351 grid-institutes:grid.27860.3b schema:alternateName Division of Medical Oncology, University of California, Davis Cancer Center, Sacramento, CA, USA
352 schema:name Division of Medical Oncology, University of California, Davis Cancer Center, Sacramento, CA, USA
353 rdf:type schema:Organization
354 grid-institutes:grid.410425.6 schema:alternateName Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA
355 Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA
356 Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA
357 schema:name Department of Biostatistics, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA
358 Department of Cancer Biology, City of Hope Comprehensive Cancer Center, 91010, Duarte, CA, USA
359 Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA
360 rdf:type schema:Organization
361 grid-institutes:grid.42505.36 schema:alternateName Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA
362 schema:name Division of Medical Oncology, University of Southern California, Norris Comprehensive Cancer Center, 90033, Los Angeles, CA, USA
363 rdf:type schema:Organization
364 grid-institutes:grid.478860.5 schema:alternateName Edward P. Evans Foundation, 20139, Casanova, VA, USA
365 schema:name Edward P. Evans Foundation, 20139, Casanova, VA, USA
366 Eisai Research Institute, 01810, Andover, MA, USA
367 rdf:type schema:Organization
368 grid-institutes:grid.48336.3a schema:alternateName Division of Cancer Treatment and Diagnosis6, National Cancer Institute, 20892, Bethesda, MD, USA
369 schema:name Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Rd., 91010, Duarte, CA, USA
370 Division of Cancer Treatment and Diagnosis6, National Cancer Institute, 20892, Bethesda, MD, USA
371 rdf:type schema:Organization
 




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


...