A prolonged methoxymorpholino doxorubicin (PNU-152243 or MMRDX) infusion schedule in patients with solid tumours: a phase 1 and pharmacokinetic study View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2000-02

AUTHORS

E Fokkema, J Verweij, A T van Oosterom, D R A Uges, R Spinelli, O Valota, E G E de Vries, H J M Groen

ABSTRACT

The aim of this phase I study was to assess feasibility, pharmacokinetics and toxicity of methoxymorpholino doxorubicin (MMRDX or PNU-152243) administered as a 3 h intravenous infusion once every 4 weeks. Fourteen patients with intrinsically anthracycline-resistant tumours received 37 cycles of MMRDX. The first cohort of patients was treated with 1 mg m(-2) of MMRDX. The next cohorts received 1.25 mg m(-2) and 1.5 mg m(-2) respectively. Common toxicity criteria (CTC) grade III/IV nausea and vomiting were observed in 1/18 cycles at 1.25 mg m(-2) and in 2/11 cycles at 1.5 mg m(-2). Transient elevation in transaminases up to CTC grade III was observed in 2/16 cycles at 1.25 mg m(-2) and 4/11 cycles at 1.5 mg m(-2). No cardiotoxicity was observed. At 1.25 mg m(-2) CTC grade IV neutropenia occurred in 1/17 cycles. At 1.5 mg m(-2) CTC grade III neutropenia was seen in 2/7 and grade IV in 3/7 evaluable cycles. Thrombocytopenia grade III was observed in 2/9 and grade IV in 1/9 evaluable cycles. One patient treated at 1.5 mg m(-2) died with neutropenic fever. Therefore, dose-limiting toxicity was reached and 1.25 mg m(-2) was considered the maximum tolerated dose for MMRDX as 3 h infusion. No tumour responses were observed. Pharmacokinetic parameters showed a rapid clearance of MMRDX from the circulation by an extensive tissue distribution. Renal excretion of the drug and its metabolite was negligible. In conclusion, prolongation of MMRDX infusion to 3 h does not improve the toxicity profile as compared with bolus administration. More... »

PAGES

767-771

References to SciGraph publications

  • 1998-01. Broad phase II and pharmacokinetic study of methoxy-morpholino doxorubicin (FCE 23762-MMRDX) in non-small-cell lung cancer, renal cancer and other solid tumour patients in BRITISH JOURNAL OF CANCER
  • 1993-01. Effects of the methoxymorpholino derivative of doxorubicin and its bioactivated form versus doxorubicin on human leukemia and lymphoma cell lines and normal bone marrow in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1985-03. Tumour cell resistance to anthracyclines — A review in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1986-04. Uptake and retention of morpholinyl anthracyclines by adriamycin-sensitive and-resistant P388 cells in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1994-07. Metabolic conversion of methoxymorpholinyl doxorubicin: from a DNA strand breaker to a DNA cross-linker in BRITISH JOURNAL OF CANCER
  • 1992-05. In vivo anti-tumour activity of FCE 23762, a methoxymorpholinyl derivative of doxorubicin active on doxorubicin-resistant tumour cells in BRITISH JOURNAL OF CANCER
  • 1993-05. Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer in CLINICAL PHARMACOLOGY & THERAPEUTICS
  • 1995-07. The role of methoxymorpholino anthracycline and cyanomorpholino anthracycline in a sensitive small-cell lung-cancer cell line and its multidrug-resistant butP-glycoprotein-negative and cisplatin-resistant counterparts in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • 1991-11. A randomized study of epirubicin at four different dose levels in advanced breast cancer. Feasibility of myelotoxicity prediction through single blood-sample measurement in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1054/bjoc.1999.0996

    DOI

    http://dx.doi.org/10.1054/bjoc.1999.0996

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033296420

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10732743


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

    JSON-LD is the canonical representation for SciGraph data.

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

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Oncology and Carcinogenesis", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Medical and Health Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Adult", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antibiotics, Antineoplastic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Antiemetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Area Under Curve", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cohort Studies", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Doxorubicin", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Drug Administration Schedule", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Male", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Middle Aged", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Neoplasms", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "University Medical Center Groningen", 
              "id": "https://www.grid.ac/institutes/grid.4494.d", 
              "name": [
                "Department of Pulmonology, Department of Pharmacy, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, Groningen, RB, 9700, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Fokkema", 
            "givenName": "E", 
            "id": "sg:person.01136230234.24", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136230234.24"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Erasmus University Medical Center", 
              "id": "https://www.grid.ac/institutes/grid.5645.2", 
              "name": [
                "Rotterdam Cancer Institute and University Hospital, Rotterdam, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Verweij", 
            "givenName": "J", 
            "id": "sg:person.01236641403.86", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236641403.86"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Universitaire Ziekenhuizen Leuven", 
              "id": "https://www.grid.ac/institutes/grid.410569.f", 
              "name": [
                "University Hospital Leuven, Belgium"
              ], 
              "type": "Organization"
            }, 
            "familyName": "van Oosterom", 
            "givenName": "A T", 
            "id": "sg:person.0653245357.14", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653245357.14"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University Medical Center Groningen", 
              "id": "https://www.grid.ac/institutes/grid.4494.d", 
              "name": [
                "Department of Pulmonology, Department of Pharmacy, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, Groningen, RB, 9700, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Uges", 
            "givenName": "D R A", 
            "id": "sg:person.014704155524.04", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014704155524.04"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Pharmacia & Upjohn, Milan, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Spinelli", 
            "givenName": "R", 
            "id": "sg:person.01127073655.98", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127073655.98"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "name": [
                "Pharmacia & Upjohn, Milan, Italy"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Valota", 
            "givenName": "O", 
            "id": "sg:person.01255260265.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255260265.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University Medical Center Groningen", 
              "id": "https://www.grid.ac/institutes/grid.4494.d", 
              "name": [
                "Department of Pulmonology, Department of Pharmacy, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, Groningen, RB, 9700, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "de Vries", 
            "givenName": "E G E", 
            "id": "sg:person.013341607157.98", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013341607157.98"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "University Medical Center Groningen", 
              "id": "https://www.grid.ac/institutes/grid.4494.d", 
              "name": [
                "Department of Pulmonology, Department of Pharmacy, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, Groningen, RB, 9700, The Netherlands"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Groen", 
            "givenName": "H J M", 
            "id": "sg:person.012466557402.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012466557402.09"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1007/bf00685824", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003009604", 
              "https://doi.org/10.1007/bf00685824"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00685824", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1003009604", 
              "https://doi.org/10.1007/bf00685824"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1998.22", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009980777", 
              "https://doi.org/10.1038/bjc.1998.22"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1998.22", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1009980777", 
              "https://doi.org/10.1038/bjc.1998.22"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00293986", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1018744514", 
              "https://doi.org/10.1007/bf00293986"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00689457", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1031853307", 
              "https://doi.org/10.1007/bf00689457"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/1097-0142(19820501)49:9<1762::aid-cncr2820490905>3.0.co;2-q", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033377280"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1002/(sici)1097-0215(19971104)73:3<362::aid-ijc10>3.0.co;2-f", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1033998359"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/clpt.1993.69", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1034898969", 
              "https://doi.org/10.1038/clpt.1993.69"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1994.253", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036523907", 
              "https://doi.org/10.1038/bjc.1994.253"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1994.253", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036523907", 
              "https://doi.org/10.1038/bjc.1994.253"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1992.148", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036554077", 
              "https://doi.org/10.1038/bjc.1992.148"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/bjc.1992.148", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1036554077", 
              "https://doi.org/10.1038/bjc.1992.148"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0378-4347(92)80431-o", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1040304566"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00434344", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041646343", 
              "https://doi.org/10.1007/bf00434344"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0006-2952(92)90666-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045353438"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0006-2952(92)90666-7", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1045353438"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00686016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046235366", 
              "https://doi.org/10.1007/bf00686016"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/bf00686016", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1046235366", 
              "https://doi.org/10.1007/bf00686016"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1016/0959-8049(93)90295-q", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049615198"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.1021/jm00371a014", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1055945343"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://doi.org/10.7326/0003-4819-96-2-133", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1073739260"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1077944709", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078406524", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078490514", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1078996354", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1079664587", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1081983012", 
            "type": "CreativeWork"
          }, 
          {
            "id": "https://app.dimensions.ai/details/publication/pub.1082489145", 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2000-02", 
        "datePublishedReg": "2000-02-01", 
        "description": "The aim of this phase I study was to assess feasibility, pharmacokinetics and toxicity of methoxymorpholino doxorubicin (MMRDX or PNU-152243) administered as a 3 h intravenous infusion once every 4 weeks. Fourteen patients with intrinsically anthracycline-resistant tumours received 37 cycles of MMRDX. The first cohort of patients was treated with 1 mg m(-2) of MMRDX. The next cohorts received 1.25 mg m(-2) and 1.5 mg m(-2) respectively. Common toxicity criteria (CTC) grade III/IV nausea and vomiting were observed in 1/18 cycles at 1.25 mg m(-2) and in 2/11 cycles at 1.5 mg m(-2). Transient elevation in transaminases up to CTC grade III was observed in 2/16 cycles at 1.25 mg m(-2) and 4/11 cycles at 1.5 mg m(-2). No cardiotoxicity was observed. At 1.25 mg m(-2) CTC grade IV neutropenia occurred in 1/17 cycles. At 1.5 mg m(-2) CTC grade III neutropenia was seen in 2/7 and grade IV in 3/7 evaluable cycles. Thrombocytopenia grade III was observed in 2/9 and grade IV in 1/9 evaluable cycles. One patient treated at 1.5 mg m(-2) died with neutropenic fever. Therefore, dose-limiting toxicity was reached and 1.25 mg m(-2) was considered the maximum tolerated dose for MMRDX as 3 h infusion. No tumour responses were observed. Pharmacokinetic parameters showed a rapid clearance of MMRDX from the circulation by an extensive tissue distribution. Renal excretion of the drug and its metabolite was negligible. In conclusion, prolongation of MMRDX infusion to 3 h does not improve the toxicity profile as compared with bolus administration.", 
        "genre": "research_article", 
        "id": "sg:pub.10.1054/bjoc.1999.0996", 
        "inLanguage": [
          "en"
        ], 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1017082", 
            "issn": [
              "0007-0920", 
              "1532-1827"
            ], 
            "name": "British Journal of Cancer", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "4", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "82"
          }
        ], 
        "name": "A prolonged methoxymorpholino doxorubicin (PNU-152243 or MMRDX) infusion schedule in patients with solid tumours: a phase 1 and pharmacokinetic study", 
        "pagination": "767-771", 
        "productId": [
          {
            "name": "readcube_id", 
            "type": "PropertyValue", 
            "value": [
              "9e9e9e4e181c9e57312d73b6e5e5a4cc39c349adcf4cc2024c3cf2e7b958696d"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "10732743"
            ]
          }, 
          {
            "name": "nlm_unique_id", 
            "type": "PropertyValue", 
            "value": [
              "0370635"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1054/bjoc.1999.0996"
            ]
          }, 
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1033296420"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1054/bjoc.1999.0996", 
          "https://app.dimensions.ai/details/publication/pub.1033296420"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2019-04-11T01:13", 
        "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/v90/0000000001_0000000264/records_8697_00000546.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374418/"
      }
    ]
     

    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.10.1054/bjoc.1999.0996'

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

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1054/bjoc.1999.0996'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1054/bjoc.1999.0996'

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

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1054/bjoc.1999.0996'


     

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

    247 TRIPLES      21 PREDICATES      64 URIs      33 LITERALS      21 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1054/bjoc.1999.0996 schema:about N20ba02acdedc44aab4abdad2422c6416
    2 N338219f2ee824a8f90b22c505b07e156
    3 N41b8037a0ee9440393ce4947180acf9a
    4 N44b216ee35c944e089ce365a8aa3a004
    5 N53119df9ba7a4aaaa9ed5f91dcea8fad
    6 N65e2e1312082451484a07fcc4bb1a9e7
    7 N7482d6abd3dc454da34a2d5016d0b556
    8 N7e9f740a716a485ea3b891af122defee
    9 N9db81876ac204acfbae5784cd33c460f
    10 Nbc963f342a204f908420b59ae8c7a384
    11 Nc772a4a913674705a83453f801d0365a
    12 Ne9ee9f6636534851bea9f38c9c24b05f
    13 anzsrc-for:11
    14 anzsrc-for:1112
    15 schema:author Nfe504690cc63440bb87789ce2b8b85d0
    16 schema:citation sg:pub.10.1007/bf00293986
    17 sg:pub.10.1007/bf00434344
    18 sg:pub.10.1007/bf00685824
    19 sg:pub.10.1007/bf00686016
    20 sg:pub.10.1007/bf00689457
    21 sg:pub.10.1038/bjc.1992.148
    22 sg:pub.10.1038/bjc.1994.253
    23 sg:pub.10.1038/bjc.1998.22
    24 sg:pub.10.1038/clpt.1993.69
    25 https://app.dimensions.ai/details/publication/pub.1077944709
    26 https://app.dimensions.ai/details/publication/pub.1078406524
    27 https://app.dimensions.ai/details/publication/pub.1078490514
    28 https://app.dimensions.ai/details/publication/pub.1078996354
    29 https://app.dimensions.ai/details/publication/pub.1079664587
    30 https://app.dimensions.ai/details/publication/pub.1081983012
    31 https://app.dimensions.ai/details/publication/pub.1082489145
    32 https://doi.org/10.1002/(sici)1097-0215(19971104)73:3<362::aid-ijc10>3.0.co;2-f
    33 https://doi.org/10.1002/1097-0142(19820501)49:9<1762::aid-cncr2820490905>3.0.co;2-q
    34 https://doi.org/10.1016/0006-2952(92)90666-7
    35 https://doi.org/10.1016/0378-4347(92)80431-o
    36 https://doi.org/10.1016/0959-8049(93)90295-q
    37 https://doi.org/10.1021/jm00371a014
    38 https://doi.org/10.7326/0003-4819-96-2-133
    39 schema:datePublished 2000-02
    40 schema:datePublishedReg 2000-02-01
    41 schema:description The aim of this phase I study was to assess feasibility, pharmacokinetics and toxicity of methoxymorpholino doxorubicin (MMRDX or PNU-152243) administered as a 3 h intravenous infusion once every 4 weeks. Fourteen patients with intrinsically anthracycline-resistant tumours received 37 cycles of MMRDX. The first cohort of patients was treated with 1 mg m(-2) of MMRDX. The next cohorts received 1.25 mg m(-2) and 1.5 mg m(-2) respectively. Common toxicity criteria (CTC) grade III/IV nausea and vomiting were observed in 1/18 cycles at 1.25 mg m(-2) and in 2/11 cycles at 1.5 mg m(-2). Transient elevation in transaminases up to CTC grade III was observed in 2/16 cycles at 1.25 mg m(-2) and 4/11 cycles at 1.5 mg m(-2). No cardiotoxicity was observed. At 1.25 mg m(-2) CTC grade IV neutropenia occurred in 1/17 cycles. At 1.5 mg m(-2) CTC grade III neutropenia was seen in 2/7 and grade IV in 3/7 evaluable cycles. Thrombocytopenia grade III was observed in 2/9 and grade IV in 1/9 evaluable cycles. One patient treated at 1.5 mg m(-2) died with neutropenic fever. Therefore, dose-limiting toxicity was reached and 1.25 mg m(-2) was considered the maximum tolerated dose for MMRDX as 3 h infusion. No tumour responses were observed. Pharmacokinetic parameters showed a rapid clearance of MMRDX from the circulation by an extensive tissue distribution. Renal excretion of the drug and its metabolite was negligible. In conclusion, prolongation of MMRDX infusion to 3 h does not improve the toxicity profile as compared with bolus administration.
    42 schema:genre research_article
    43 schema:inLanguage en
    44 schema:isAccessibleForFree true
    45 schema:isPartOf N78d37254c23b4baba4b12356ab98b49e
    46 Ncbb31be7e98e4997979770491e52f0ba
    47 sg:journal.1017082
    48 schema:name A prolonged methoxymorpholino doxorubicin (PNU-152243 or MMRDX) infusion schedule in patients with solid tumours: a phase 1 and pharmacokinetic study
    49 schema:pagination 767-771
    50 schema:productId N262b755ed136441db0604928fb49ade4
    51 Nb42e8ebd21924eed8ed952573f8e31ec
    52 Ndcce9d6e52314f5092d849229e6ead05
    53 Nefbbdc203cc54e61985011e5765f3873
    54 Nefc1c84ef0114d39818e42ecf4562078
    55 schema:sameAs https://app.dimensions.ai/details/publication/pub.1033296420
    56 https://doi.org/10.1054/bjoc.1999.0996
    57 schema:sdDatePublished 2019-04-11T01:13
    58 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    59 schema:sdPublisher N84b240240f25490186d069f774dd2880
    60 schema:url http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374418/
    61 sgo:license sg:explorer/license/
    62 sgo:sdDataset articles
    63 rdf:type schema:ScholarlyArticle
    64 N0e4882af077e4db29dcbb5b876eb32fd rdf:first sg:person.013341607157.98
    65 rdf:rest N83c69220c3f845c2b01d995a2a7ef82d
    66 N20ba02acdedc44aab4abdad2422c6416 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    67 schema:name Aged
    68 rdf:type schema:DefinedTerm
    69 N262b755ed136441db0604928fb49ade4 schema:name dimensions_id
    70 schema:value pub.1033296420
    71 rdf:type schema:PropertyValue
    72 N313eb74d196b446f9194a2c7a37e3466 rdf:first sg:person.01236641403.86
    73 rdf:rest N6f980a69807c4584b8b309243fa60bdd
    74 N338219f2ee824a8f90b22c505b07e156 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    75 schema:name Area Under Curve
    76 rdf:type schema:DefinedTerm
    77 N41b8037a0ee9440393ce4947180acf9a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    78 schema:name Adult
    79 rdf:type schema:DefinedTerm
    80 N44b216ee35c944e089ce365a8aa3a004 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    81 schema:name Drug Administration Schedule
    82 rdf:type schema:DefinedTerm
    83 N53119df9ba7a4aaaa9ed5f91dcea8fad schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    84 schema:name Doxorubicin
    85 rdf:type schema:DefinedTerm
    86 N65e2e1312082451484a07fcc4bb1a9e7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    87 schema:name Antibiotics, Antineoplastic
    88 rdf:type schema:DefinedTerm
    89 N6cdfd9e17c934cf584a75662c1a55bf4 rdf:first sg:person.01255260265.66
    90 rdf:rest N0e4882af077e4db29dcbb5b876eb32fd
    91 N6f980a69807c4584b8b309243fa60bdd rdf:first sg:person.0653245357.14
    92 rdf:rest N933315c2dce24ad89f081b4b109f7e80
    93 N7482d6abd3dc454da34a2d5016d0b556 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    94 schema:name Neoplasms
    95 rdf:type schema:DefinedTerm
    96 N78d37254c23b4baba4b12356ab98b49e schema:issueNumber 4
    97 rdf:type schema:PublicationIssue
    98 N7e9f740a716a485ea3b891af122defee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    99 schema:name Antiemetics
    100 rdf:type schema:DefinedTerm
    101 N83c69220c3f845c2b01d995a2a7ef82d rdf:first sg:person.012466557402.09
    102 rdf:rest rdf:nil
    103 N84b240240f25490186d069f774dd2880 schema:name Springer Nature - SN SciGraph project
    104 rdf:type schema:Organization
    105 N8a61643d54bc4bcb8f73b4b17c12f098 rdf:first sg:person.01127073655.98
    106 rdf:rest N6cdfd9e17c934cf584a75662c1a55bf4
    107 N933315c2dce24ad89f081b4b109f7e80 rdf:first sg:person.014704155524.04
    108 rdf:rest N8a61643d54bc4bcb8f73b4b17c12f098
    109 N9db81876ac204acfbae5784cd33c460f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    110 schema:name Cohort Studies
    111 rdf:type schema:DefinedTerm
    112 N9e48df0b76c14167baf8b40ba29d34d8 schema:name Pharmacia & Upjohn, Milan, Italy
    113 rdf:type schema:Organization
    114 Nb42e8ebd21924eed8ed952573f8e31ec schema:name doi
    115 schema:value 10.1054/bjoc.1999.0996
    116 rdf:type schema:PropertyValue
    117 Nb9c9dab922d74661bd3581f4201795fd schema:name Pharmacia & Upjohn, Milan, Italy
    118 rdf:type schema:Organization
    119 Nbc963f342a204f908420b59ae8c7a384 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    120 schema:name Humans
    121 rdf:type schema:DefinedTerm
    122 Nc772a4a913674705a83453f801d0365a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    123 schema:name Male
    124 rdf:type schema:DefinedTerm
    125 Ncbb31be7e98e4997979770491e52f0ba schema:volumeNumber 82
    126 rdf:type schema:PublicationVolume
    127 Ndcce9d6e52314f5092d849229e6ead05 schema:name nlm_unique_id
    128 schema:value 0370635
    129 rdf:type schema:PropertyValue
    130 Ne9ee9f6636534851bea9f38c9c24b05f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    131 schema:name Middle Aged
    132 rdf:type schema:DefinedTerm
    133 Nefbbdc203cc54e61985011e5765f3873 schema:name pubmed_id
    134 schema:value 10732743
    135 rdf:type schema:PropertyValue
    136 Nefc1c84ef0114d39818e42ecf4562078 schema:name readcube_id
    137 schema:value 9e9e9e4e181c9e57312d73b6e5e5a4cc39c349adcf4cc2024c3cf2e7b958696d
    138 rdf:type schema:PropertyValue
    139 Nfe504690cc63440bb87789ce2b8b85d0 rdf:first sg:person.01136230234.24
    140 rdf:rest N313eb74d196b446f9194a2c7a37e3466
    141 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
    142 schema:name Medical and Health Sciences
    143 rdf:type schema:DefinedTerm
    144 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
    145 schema:name Oncology and Carcinogenesis
    146 rdf:type schema:DefinedTerm
    147 sg:journal.1017082 schema:issn 0007-0920
    148 1532-1827
    149 schema:name British Journal of Cancer
    150 rdf:type schema:Periodical
    151 sg:person.01127073655.98 schema:affiliation Nb9c9dab922d74661bd3581f4201795fd
    152 schema:familyName Spinelli
    153 schema:givenName R
    154 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01127073655.98
    155 rdf:type schema:Person
    156 sg:person.01136230234.24 schema:affiliation https://www.grid.ac/institutes/grid.4494.d
    157 schema:familyName Fokkema
    158 schema:givenName E
    159 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136230234.24
    160 rdf:type schema:Person
    161 sg:person.01236641403.86 schema:affiliation https://www.grid.ac/institutes/grid.5645.2
    162 schema:familyName Verweij
    163 schema:givenName J
    164 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01236641403.86
    165 rdf:type schema:Person
    166 sg:person.012466557402.09 schema:affiliation https://www.grid.ac/institutes/grid.4494.d
    167 schema:familyName Groen
    168 schema:givenName H J M
    169 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.012466557402.09
    170 rdf:type schema:Person
    171 sg:person.01255260265.66 schema:affiliation N9e48df0b76c14167baf8b40ba29d34d8
    172 schema:familyName Valota
    173 schema:givenName O
    174 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01255260265.66
    175 rdf:type schema:Person
    176 sg:person.013341607157.98 schema:affiliation https://www.grid.ac/institutes/grid.4494.d
    177 schema:familyName de Vries
    178 schema:givenName E G E
    179 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013341607157.98
    180 rdf:type schema:Person
    181 sg:person.014704155524.04 schema:affiliation https://www.grid.ac/institutes/grid.4494.d
    182 schema:familyName Uges
    183 schema:givenName D R A
    184 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014704155524.04
    185 rdf:type schema:Person
    186 sg:person.0653245357.14 schema:affiliation https://www.grid.ac/institutes/grid.410569.f
    187 schema:familyName van Oosterom
    188 schema:givenName A T
    189 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0653245357.14
    190 rdf:type schema:Person
    191 sg:pub.10.1007/bf00293986 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018744514
    192 https://doi.org/10.1007/bf00293986
    193 rdf:type schema:CreativeWork
    194 sg:pub.10.1007/bf00434344 schema:sameAs https://app.dimensions.ai/details/publication/pub.1041646343
    195 https://doi.org/10.1007/bf00434344
    196 rdf:type schema:CreativeWork
    197 sg:pub.10.1007/bf00685824 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003009604
    198 https://doi.org/10.1007/bf00685824
    199 rdf:type schema:CreativeWork
    200 sg:pub.10.1007/bf00686016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046235366
    201 https://doi.org/10.1007/bf00686016
    202 rdf:type schema:CreativeWork
    203 sg:pub.10.1007/bf00689457 schema:sameAs https://app.dimensions.ai/details/publication/pub.1031853307
    204 https://doi.org/10.1007/bf00689457
    205 rdf:type schema:CreativeWork
    206 sg:pub.10.1038/bjc.1992.148 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036554077
    207 https://doi.org/10.1038/bjc.1992.148
    208 rdf:type schema:CreativeWork
    209 sg:pub.10.1038/bjc.1994.253 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036523907
    210 https://doi.org/10.1038/bjc.1994.253
    211 rdf:type schema:CreativeWork
    212 sg:pub.10.1038/bjc.1998.22 schema:sameAs https://app.dimensions.ai/details/publication/pub.1009980777
    213 https://doi.org/10.1038/bjc.1998.22
    214 rdf:type schema:CreativeWork
    215 sg:pub.10.1038/clpt.1993.69 schema:sameAs https://app.dimensions.ai/details/publication/pub.1034898969
    216 https://doi.org/10.1038/clpt.1993.69
    217 rdf:type schema:CreativeWork
    218 https://app.dimensions.ai/details/publication/pub.1077944709 schema:CreativeWork
    219 https://app.dimensions.ai/details/publication/pub.1078406524 schema:CreativeWork
    220 https://app.dimensions.ai/details/publication/pub.1078490514 schema:CreativeWork
    221 https://app.dimensions.ai/details/publication/pub.1078996354 schema:CreativeWork
    222 https://app.dimensions.ai/details/publication/pub.1079664587 schema:CreativeWork
    223 https://app.dimensions.ai/details/publication/pub.1081983012 schema:CreativeWork
    224 https://app.dimensions.ai/details/publication/pub.1082489145 schema:CreativeWork
    225 https://doi.org/10.1002/(sici)1097-0215(19971104)73:3<362::aid-ijc10>3.0.co;2-f schema:sameAs https://app.dimensions.ai/details/publication/pub.1033998359
    226 rdf:type schema:CreativeWork
    227 https://doi.org/10.1002/1097-0142(19820501)49:9<1762::aid-cncr2820490905>3.0.co;2-q schema:sameAs https://app.dimensions.ai/details/publication/pub.1033377280
    228 rdf:type schema:CreativeWork
    229 https://doi.org/10.1016/0006-2952(92)90666-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045353438
    230 rdf:type schema:CreativeWork
    231 https://doi.org/10.1016/0378-4347(92)80431-o schema:sameAs https://app.dimensions.ai/details/publication/pub.1040304566
    232 rdf:type schema:CreativeWork
    233 https://doi.org/10.1016/0959-8049(93)90295-q schema:sameAs https://app.dimensions.ai/details/publication/pub.1049615198
    234 rdf:type schema:CreativeWork
    235 https://doi.org/10.1021/jm00371a014 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055945343
    236 rdf:type schema:CreativeWork
    237 https://doi.org/10.7326/0003-4819-96-2-133 schema:sameAs https://app.dimensions.ai/details/publication/pub.1073739260
    238 rdf:type schema:CreativeWork
    239 https://www.grid.ac/institutes/grid.410569.f schema:alternateName Universitaire Ziekenhuizen Leuven
    240 schema:name University Hospital Leuven, Belgium
    241 rdf:type schema:Organization
    242 https://www.grid.ac/institutes/grid.4494.d schema:alternateName University Medical Center Groningen
    243 schema:name Department of Pulmonology, Department of Pharmacy, Department of Internal Medicine, University Hospital Groningen, PO Box 30.001, Groningen, RB, 9700, The Netherlands
    244 rdf:type schema:Organization
    245 https://www.grid.ac/institutes/grid.5645.2 schema:alternateName Erasmus University Medical Center
    246 schema:name Rotterdam Cancer Institute and University Hospital, Rotterdam, The Netherlands
    247 rdf:type schema:Organization
     




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


    ...