Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-09-02

AUTHORS

S Rao, N Starling, D Cunningham, M Benson, A Wotherspoon, C Lüpfert, R Kurek, J Oates, J Baselga, A Hill

ABSTRACT

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m−2, cisplatin 60 mg m−2 on day 1 and capecitabine 1000 mg m−2 daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43–82), disease stabilisation of 25% (95% CI: 11–47) and a disease control rate (CR+PR+SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3. More... »

PAGES

868-874

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6604622

DOI

http://dx.doi.org/10.1038/sj.bjc.6604622

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052205307

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19238629


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/2008/1103", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Clinical Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Adenocarcinoma", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibodies, Monoclonal", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antibodies, Monoclonal, Humanized", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Antineoplastic Combined Chemotherapy Protocols", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Capecitabine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cisplatin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Deoxycytidine", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Disease-Free Survival", 
        "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 Therapy, Combination", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Epirubicin", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "ErbB Receptors", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Esophageal Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Esophagogastric Junction", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Female", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Fluorouracil", 
        "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": "Maximum Tolerated Dose", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Middle Aged", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Neoplasm Staging", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Stomach Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Survival Rate", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Tissue Distribution", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Treatment Outcome", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rao", 
        "givenName": "S", 
        "id": "sg:person.01321127272.55", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01321127272.55"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Starling", 
        "givenName": "N", 
        "id": "sg:person.01136565472.17", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136565472.17"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cunningham", 
        "givenName": "D", 
        "id": "sg:person.01320161130.16", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320161130.16"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Benson", 
        "givenName": "M", 
        "id": "sg:person.01265070333.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01265070333.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wotherspoon", 
        "givenName": "A", 
        "id": "sg:person.01000107664.44", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01000107664.44"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Merck KGaA, Darmstadt, Germany", 
          "id": "http://www.grid.ac/institutes/grid.39009.33", 
          "name": [
            "Merck KGaA, Darmstadt, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "L\u00fcpfert", 
        "givenName": "C", 
        "id": "sg:person.01032121547.69", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01032121547.69"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Merck KGaA, Darmstadt, Germany", 
          "id": "http://www.grid.ac/institutes/grid.39009.33", 
          "name": [
            "Merck KGaA, Darmstadt, Germany"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Kurek", 
        "givenName": "R", 
        "id": "sg:person.0602351767.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0602351767.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Oates", 
        "givenName": "J", 
        "id": "sg:person.01270334576.91", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270334576.91"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "University of Hebron, Barcelona, Spain", 
          "id": "http://www.grid.ac/institutes/None", 
          "name": [
            "University of Hebron, Barcelona, Spain"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Baselga", 
        "givenName": "J", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Medicine, Royal Marsden Hospital, Surrey, UK", 
          "id": "http://www.grid.ac/institutes/grid.424926.f", 
          "name": [
            "Department of Medicine, Royal Marsden Hospital, Surrey, UK"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hill", 
        "givenName": "A", 
        "id": "sg:person.01027613160.71", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01027613160.71"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/sj.bjc.6603083", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014201452", 
          "https://doi.org/10.1038/sj.bjc.6603083"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s002620050475", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1023193006", 
          "https://doi.org/10.1007/s002620050475"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/bjc.1995.114", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030614602", 
          "https://doi.org/10.1038/bjc.1995.114"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6602572", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003250351", 
          "https://doi.org/10.1038/sj.bjc.6602572"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/35004044", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1050684640", 
          "https://doi.org/10.1038/35004044"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6690350", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1045469768", 
          "https://doi.org/10.1038/sj.bjc.6690350"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2008-09-02", 
    "datePublishedReg": "2008-09-02", 
    "description": "To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800\u2009mg weekly and 1200\u2009mg every 3 weeks combined with ECX (epirubicin 50\u2009mg\u2009m\u22122, cisplatin 60\u2009mg\u2009m\u22122 on day 1 and capecitabine 1000\u2009mg\u2009m\u22122 daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200\u2009mg matuzumab every 3 weeks and thus 800\u2009mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43\u201382), disease stabilisation of 25% (95% CI: 11\u201347) and a disease control rate (CR+PR+SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800\u2009mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.", 
    "genre": "article", 
    "id": "sg:pub.10.1038/sj.bjc.6604622", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1017082", 
        "issn": [
          "0007-0920", 
          "1532-1827"
        ], 
        "name": "British Journal of Cancer", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "6", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "99"
      }
    ], 
    "keywords": [
      "maximum-tolerated dose", 
      "different dose levels", 
      "advanced oesophagogastric cancer", 
      "epidermal growth factor receptor", 
      "dose-limiting toxicity", 
      "oesophagogastric cancer", 
      "skin biopsies", 
      "main dose-limiting toxicity", 
      "phase I", 
      "grade 3 lethargy", 
      "objective response rate", 
      "disease control rate", 
      "first-line treatment", 
      "serial skin biopsies", 
      "phosphorylation of EGFR", 
      "growth factor receptor", 
      "common toxicities", 
      "disease stabilisation", 
      "unacceptable toxicity", 
      "untreated patients", 
      "escalation study", 
      "control rate", 
      "disease progression", 
      "pharmacodynamic studies", 
      "pharmacokinetic evaluation", 
      "dose levels", 
      "response rate", 
      "patients", 
      "matuzumab", 
      "antitumour activity", 
      "STAT-3", 
      "EGFR pathway", 
      "factor receptor", 
      "capecitabine", 
      "weekly", 
      "biopsy", 
      "epirubicin", 
      "cancer", 
      "cisplatin", 
      "weeks", 
      "toxicity", 
      "tolerability", 
      "nausea", 
      "rash", 
      "coadministration", 
      "diarrhea", 
      "pharmacodynamics", 
      "stomatitis", 
      "lethargy", 
      "pharmacokinetics", 
      "phosphorylation", 
      "dose", 
      "doses", 
      "progression", 
      "receptors", 
      "efficacy", 
      "ECX", 
      "treatment", 
      "inhibition", 
      "study", 
      "MAPK", 
      "exposure", 
      "rate", 
      "safety", 
      "pathway", 
      "levels", 
      "evaluation", 
      "activity", 
      "combination", 
      "stabilisation", 
      "cycle", 
      "maximum"
    ], 
    "name": "Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer", 
    "pagination": "868-874", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1052205307"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/sj.bjc.6604622"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "19238629"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/sj.bjc.6604622", 
      "https://app.dimensions.ai/details/publication/pub.1052205307"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-10-01T06:34", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20221001/entities/gbq_results/article/article_473.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1038/sj.bjc.6604622"
  }
]
 

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.10.1038/sj.bjc.6604622'

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

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6604622'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6604622'

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

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/sj.bjc.6604622'


 

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

325 TRIPLES      21 PREDICATES      128 URIs      114 LITERALS      32 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/sj.bjc.6604622 schema:about N116d5e9ea6a247c6b11b351d4a80e333
2 N12a3f909a9d145b18cb4bc77c9a2037c
3 N1be6431b2b974e7db939178494c9f748
4 N2d8d76d4353048329ad4b14398a1608f
5 N32898ca806a14b20a40e13881f43c0fe
6 N35b7f931906c4392ae4e18e039949437
7 N4e6f47d34ddd4172b5a72166f03361ee
8 N55d5da6d11424ce7a33c495e14516d66
9 N5bab654c725d4c2ba0b4567b1ee49427
10 N5ca2d74f9782422b948ae87bd349db6e
11 N61b6e62d6cec4e83848d8488b55a1a24
12 N6e71ac6edcb9457096ee467b827eb08c
13 N71092d58c8ab481cb1ee36fbba815a55
14 N74f19a993c294d6cb4f46055ba109af4
15 N81bcc8cd0a6e4f598f4297a851364795
16 N8b2f51c163db40659484951bc4abbad4
17 N8c47dfe46ce8406da48b3af009b32a57
18 Nb53fb368cd084bc3bf6ac5cdb4af7d96
19 Nb8cd1b7ca8544ca6957aef10851a8d5e
20 Nbd70f17bfcdf4da9a45750d9337abd4a
21 Nd3018c1eb0e6438eb36b9a0c1f09b74d
22 Ne5c7a44aa23544a2b3bda5ff8486174c
23 Ne7a0241fa0d9437a8991ae4bfb1d0252
24 Nf8b3e4aab29c43bf91fc88fc681e423e
25 Nfbc2543c530345da9ba8cbb1e94626be
26 anzsrc-for:11
27 anzsrc-for:1103
28 schema:author N8d14eeff109e4dcb894067eae9330d8c
29 schema:citation sg:pub.10.1007/s002620050475
30 sg:pub.10.1038/35004044
31 sg:pub.10.1038/bjc.1995.114
32 sg:pub.10.1038/sj.bjc.6602572
33 sg:pub.10.1038/sj.bjc.6603083
34 sg:pub.10.1038/sj.bjc.6690350
35 schema:datePublished 2008-09-02
36 schema:datePublishedReg 2008-09-02
37 schema:description To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m−2, cisplatin 60 mg m−2 on day 1 and capecitabine 1000 mg m−2 daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43–82), disease stabilisation of 25% (95% CI: 11–47) and a disease control rate (CR+PR+SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.
38 schema:genre article
39 schema:isAccessibleForFree true
40 schema:isPartOf N30ec694da916438d8388952817c247bf
41 N8c4c69054f30440dbd268314f36135ea
42 sg:journal.1017082
43 schema:keywords ECX
44 EGFR pathway
45 MAPK
46 STAT-3
47 activity
48 advanced oesophagogastric cancer
49 antitumour activity
50 biopsy
51 cancer
52 capecitabine
53 cisplatin
54 coadministration
55 combination
56 common toxicities
57 control rate
58 cycle
59 diarrhea
60 different dose levels
61 disease control rate
62 disease progression
63 disease stabilisation
64 dose
65 dose levels
66 dose-limiting toxicity
67 doses
68 efficacy
69 epidermal growth factor receptor
70 epirubicin
71 escalation study
72 evaluation
73 exposure
74 factor receptor
75 first-line treatment
76 grade 3 lethargy
77 growth factor receptor
78 inhibition
79 lethargy
80 levels
81 main dose-limiting toxicity
82 matuzumab
83 maximum
84 maximum-tolerated dose
85 nausea
86 objective response rate
87 oesophagogastric cancer
88 pathway
89 patients
90 pharmacodynamic studies
91 pharmacodynamics
92 pharmacokinetic evaluation
93 pharmacokinetics
94 phase I
95 phosphorylation
96 phosphorylation of EGFR
97 progression
98 rash
99 rate
100 receptors
101 response rate
102 safety
103 serial skin biopsies
104 skin biopsies
105 stabilisation
106 stomatitis
107 study
108 tolerability
109 toxicity
110 treatment
111 unacceptable toxicity
112 untreated patients
113 weekly
114 weeks
115 schema:name Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer
116 schema:pagination 868-874
117 schema:productId Nbbc4f3bbe925459588f0c31b3f167d83
118 Nbcc57bdc7a2e4080a2dd80ea4b033560
119 Nc32d6913d32546bca25a5a580f59adbf
120 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052205307
121 https://doi.org/10.1038/sj.bjc.6604622
122 schema:sdDatePublished 2022-10-01T06:34
123 schema:sdLicense https://scigraph.springernature.com/explorer/license/
124 schema:sdPublisher Ndc1f69ef617345229ac1e6f3a63dfcce
125 schema:url https://doi.org/10.1038/sj.bjc.6604622
126 sgo:license sg:explorer/license/
127 sgo:sdDataset articles
128 rdf:type schema:ScholarlyArticle
129 N116d5e9ea6a247c6b11b351d4a80e333 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
130 schema:name Esophageal Neoplasms
131 rdf:type schema:DefinedTerm
132 N12a3f909a9d145b18cb4bc77c9a2037c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
133 schema:name Male
134 rdf:type schema:DefinedTerm
135 N15524969ae77485cb175f19da712a485 rdf:first sg:person.01265070333.06
136 rdf:rest N7b7eeca3af5b45fa87962a98df0ed13f
137 N1be6431b2b974e7db939178494c9f748 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
138 schema:name Female
139 rdf:type schema:DefinedTerm
140 N2d8d76d4353048329ad4b14398a1608f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
141 schema:name Antibodies, Monoclonal, Humanized
142 rdf:type schema:DefinedTerm
143 N309b77c8d65c4177bcf87fb69600526a rdf:first sg:person.01136565472.17
144 rdf:rest N59b39821114c4cd6a6ab5a2af2f4238a
145 N30ec694da916438d8388952817c247bf schema:volumeNumber 99
146 rdf:type schema:PublicationVolume
147 N32898ca806a14b20a40e13881f43c0fe schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
148 schema:name Stomach Neoplasms
149 rdf:type schema:DefinedTerm
150 N35b7f931906c4392ae4e18e039949437 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
151 schema:name Disease-Free Survival
152 rdf:type schema:DefinedTerm
153 N4e6f47d34ddd4172b5a72166f03361ee schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
154 schema:name Cisplatin
155 rdf:type schema:DefinedTerm
156 N55d5da6d11424ce7a33c495e14516d66 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Tissue Distribution
158 rdf:type schema:DefinedTerm
159 N59b39821114c4cd6a6ab5a2af2f4238a rdf:first sg:person.01320161130.16
160 rdf:rest N15524969ae77485cb175f19da712a485
161 N5bab654c725d4c2ba0b4567b1ee49427 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
162 schema:name Esophagogastric Junction
163 rdf:type schema:DefinedTerm
164 N5ca2d74f9782422b948ae87bd349db6e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
165 schema:name Drug Therapy, Combination
166 rdf:type schema:DefinedTerm
167 N61b6e62d6cec4e83848d8488b55a1a24 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
168 schema:name ErbB Receptors
169 rdf:type schema:DefinedTerm
170 N6e71ac6edcb9457096ee467b827eb08c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
171 schema:name Neoplasm Staging
172 rdf:type schema:DefinedTerm
173 N71092d58c8ab481cb1ee36fbba815a55 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
174 schema:name Antibodies, Monoclonal
175 rdf:type schema:DefinedTerm
176 N74f19a993c294d6cb4f46055ba109af4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
177 schema:name Survival Rate
178 rdf:type schema:DefinedTerm
179 N7b7eeca3af5b45fa87962a98df0ed13f rdf:first sg:person.01000107664.44
180 rdf:rest N849f9906b01441cc8b045290acb96294
181 N81bcc8cd0a6e4f598f4297a851364795 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
182 schema:name Capecitabine
183 rdf:type schema:DefinedTerm
184 N849f9906b01441cc8b045290acb96294 rdf:first sg:person.01032121547.69
185 rdf:rest Ncb83c99a807a48a8a7b635def6f72237
186 N8b2f51c163db40659484951bc4abbad4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
187 schema:name Epirubicin
188 rdf:type schema:DefinedTerm
189 N8c47dfe46ce8406da48b3af009b32a57 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
190 schema:name Adenocarcinoma
191 rdf:type schema:DefinedTerm
192 N8c4c69054f30440dbd268314f36135ea schema:issueNumber 6
193 rdf:type schema:PublicationIssue
194 N8d14eeff109e4dcb894067eae9330d8c rdf:first sg:person.01321127272.55
195 rdf:rest N309b77c8d65c4177bcf87fb69600526a
196 N9dd5887944ad49e2a4ea0b370a51e413 schema:affiliation grid-institutes:None
197 schema:familyName Baselga
198 schema:givenName J
199 rdf:type schema:Person
200 Na0e1e9e3d8474abf90a6b6c3c0d08e00 rdf:first sg:person.01270334576.91
201 rdf:rest Neef88a5fb16f48f28eec4fecfaf5a5fa
202 Nb53fb368cd084bc3bf6ac5cdb4af7d96 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
203 schema:name Middle Aged
204 rdf:type schema:DefinedTerm
205 Nb8cd1b7ca8544ca6957aef10851a8d5e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
206 schema:name Humans
207 rdf:type schema:DefinedTerm
208 Nbbc4f3bbe925459588f0c31b3f167d83 schema:name dimensions_id
209 schema:value pub.1052205307
210 rdf:type schema:PropertyValue
211 Nbcc57bdc7a2e4080a2dd80ea4b033560 schema:name doi
212 schema:value 10.1038/sj.bjc.6604622
213 rdf:type schema:PropertyValue
214 Nbd70f17bfcdf4da9a45750d9337abd4a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
215 schema:name Dose-Response Relationship, Drug
216 rdf:type schema:DefinedTerm
217 Nc32d6913d32546bca25a5a580f59adbf schema:name pubmed_id
218 schema:value 19238629
219 rdf:type schema:PropertyValue
220 Ncb83c99a807a48a8a7b635def6f72237 rdf:first sg:person.0602351767.21
221 rdf:rest Na0e1e9e3d8474abf90a6b6c3c0d08e00
222 Nd3018c1eb0e6438eb36b9a0c1f09b74d schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
223 schema:name Maximum Tolerated Dose
224 rdf:type schema:DefinedTerm
225 Nd6d775f1ce8640a7bd2e948a46dab8aa rdf:first sg:person.01027613160.71
226 rdf:rest rdf:nil
227 Ndc1f69ef617345229ac1e6f3a63dfcce schema:name Springer Nature - SN SciGraph project
228 rdf:type schema:Organization
229 Ne5c7a44aa23544a2b3bda5ff8486174c schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
230 schema:name Treatment Outcome
231 rdf:type schema:DefinedTerm
232 Ne7a0241fa0d9437a8991ae4bfb1d0252 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
233 schema:name Deoxycytidine
234 rdf:type schema:DefinedTerm
235 Neef88a5fb16f48f28eec4fecfaf5a5fa rdf:first N9dd5887944ad49e2a4ea0b370a51e413
236 rdf:rest Nd6d775f1ce8640a7bd2e948a46dab8aa
237 Nf8b3e4aab29c43bf91fc88fc681e423e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
238 schema:name Antineoplastic Combined Chemotherapy Protocols
239 rdf:type schema:DefinedTerm
240 Nfbc2543c530345da9ba8cbb1e94626be schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
241 schema:name Fluorouracil
242 rdf:type schema:DefinedTerm
243 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
244 schema:name Medical and Health Sciences
245 rdf:type schema:DefinedTerm
246 anzsrc-for:1103 schema:inDefinedTermSet anzsrc-for:
247 schema:name Clinical Sciences
248 rdf:type schema:DefinedTerm
249 sg:journal.1017082 schema:issn 0007-0920
250 1532-1827
251 schema:name British Journal of Cancer
252 schema:publisher Springer Nature
253 rdf:type schema:Periodical
254 sg:person.01000107664.44 schema:affiliation grid-institutes:grid.424926.f
255 schema:familyName Wotherspoon
256 schema:givenName A
257 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01000107664.44
258 rdf:type schema:Person
259 sg:person.01027613160.71 schema:affiliation grid-institutes:grid.424926.f
260 schema:familyName Hill
261 schema:givenName A
262 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01027613160.71
263 rdf:type schema:Person
264 sg:person.01032121547.69 schema:affiliation grid-institutes:grid.39009.33
265 schema:familyName Lüpfert
266 schema:givenName C
267 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01032121547.69
268 rdf:type schema:Person
269 sg:person.01136565472.17 schema:affiliation grid-institutes:grid.424926.f
270 schema:familyName Starling
271 schema:givenName N
272 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01136565472.17
273 rdf:type schema:Person
274 sg:person.01265070333.06 schema:affiliation grid-institutes:grid.424926.f
275 schema:familyName Benson
276 schema:givenName M
277 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01265070333.06
278 rdf:type schema:Person
279 sg:person.01270334576.91 schema:affiliation grid-institutes:grid.424926.f
280 schema:familyName Oates
281 schema:givenName J
282 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01270334576.91
283 rdf:type schema:Person
284 sg:person.01320161130.16 schema:affiliation grid-institutes:grid.424926.f
285 schema:familyName Cunningham
286 schema:givenName D
287 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01320161130.16
288 rdf:type schema:Person
289 sg:person.01321127272.55 schema:affiliation grid-institutes:grid.424926.f
290 schema:familyName Rao
291 schema:givenName S
292 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01321127272.55
293 rdf:type schema:Person
294 sg:person.0602351767.21 schema:affiliation grid-institutes:grid.39009.33
295 schema:familyName Kurek
296 schema:givenName R
297 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0602351767.21
298 rdf:type schema:Person
299 sg:pub.10.1007/s002620050475 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023193006
300 https://doi.org/10.1007/s002620050475
301 rdf:type schema:CreativeWork
302 sg:pub.10.1038/35004044 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050684640
303 https://doi.org/10.1038/35004044
304 rdf:type schema:CreativeWork
305 sg:pub.10.1038/bjc.1995.114 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030614602
306 https://doi.org/10.1038/bjc.1995.114
307 rdf:type schema:CreativeWork
308 sg:pub.10.1038/sj.bjc.6602572 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003250351
309 https://doi.org/10.1038/sj.bjc.6602572
310 rdf:type schema:CreativeWork
311 sg:pub.10.1038/sj.bjc.6603083 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014201452
312 https://doi.org/10.1038/sj.bjc.6603083
313 rdf:type schema:CreativeWork
314 sg:pub.10.1038/sj.bjc.6690350 schema:sameAs https://app.dimensions.ai/details/publication/pub.1045469768
315 https://doi.org/10.1038/sj.bjc.6690350
316 rdf:type schema:CreativeWork
317 grid-institutes:None schema:alternateName University of Hebron, Barcelona, Spain
318 schema:name University of Hebron, Barcelona, Spain
319 rdf:type schema:Organization
320 grid-institutes:grid.39009.33 schema:alternateName Merck KGaA, Darmstadt, Germany
321 schema:name Merck KGaA, Darmstadt, Germany
322 rdf:type schema:Organization
323 grid-institutes:grid.424926.f schema:alternateName Department of Medicine, Royal Marsden Hospital, Surrey, UK
324 schema:name Department of Medicine, Royal Marsden Hospital, Surrey, UK
325 rdf:type schema:Organization
 




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


...