• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsProfilesView

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Baselga, Jose
    Rischin, Danny
    Ranson, Malcolm R
    Calvert, A Hilary
    Raymond, Eric
    Kieback, Dirk
    Kaye, Stan B
    Gianni, L
    Harris, A
    Björk-Eriksson, Thomas
    Averbuch, Steven D
    Feyereislova, Andrea
    Swaisland, Helen C
    Rojo, F
    Albanell, Joan
    Show allShow less
    Affiliation
    Vall d'Hebron University Hospital, Barcelona, Spain. baselga@hg.vhebron.es
    Issue Date
    2002-11-01
    
    Metadata
    Show full item record
    Abstract
    PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non-small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for >or= 3 months; seven of these patients remained on study drug for >or= 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
    Citation
    Phase I safety, pharmacokinetic, and pharmacodynamic trial of ZD1839, a selective oral epidermal growth factor receptor tyrosine kinase inhibitor, in patients with five selected solid tumor types. 2002, 20 (21):4292-302 J. Clin. Oncol.
    Journal
    Journal of Clinical Oncology
    URI
    http://hdl.handle.net/10541/80218
    PubMed ID
    12409327
    Type
    Article
    Language
    en
    ISSN
    0732-183X
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 is generally well-tolerated and has activity in non-small-cell lung cancer and other solid tumors: results of a phase I trial.
    • Authors: Herbst RS, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Baselga J, Rojo F, Hong WK, Swaisland H, Averbuch SD, Ochs J, LoRusso PM
    • Issue date: 2002 Sep 15
    • Phase I studies of ZD1839 in patients with common solid tumors.
    • Authors: Lorusso PM
    • Issue date: 2003 Feb
    • ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.
    • Authors: Ranson M, Hammond LA, Ferry D, Kris M, Tullo A, Murray PI, Miller V, Averbuch S, Ochs J, Morris C, Feyereislova A, Swaisland H, Rowinsky EK
    • Issue date: 2002 May 1
    • Gefitinib (Iressa, ZD1839): a novel targeted approach for the treatment of solid tumors.
    • Authors: Von Pawel J
    • Issue date: 2004 May 1
    • Improvements in quality of life and disease-related symptoms in phase I trials of the selective oral epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in non-small cell lung cancer and other solid tumors.
    • Authors: LoRusso PM, Herbst RS, Rischin D, Ranson M, Calvert H, Raymond E, Kieback D, Kaye S, Gianni L, Harris A, Bjork T, Maddox AM, Rothenberg ML, Small EJ, Rubin EH, Feyereislova A, Heyes A, Averbuch SD, Ochs J, Baselga J
    • Issue date: 2003 Jun

    Related items

    Showing items related by title, author, creator and subject.

    • Thumbnail

      Treatment for non small cell lung cancer, small cell lung cancer and pleural mesothelioma within the EORTC Lung Cancer Group: past, present and future.

      O'Brien, M; van Meerbeeck, J; Surmont, V; Faivre-Finn, Corinne (2012)
    • Thumbnail

      Ovarian cancer among 8,005 women from a breast cancer family history clinic: no increased risk of invasive ovarian cancer in families testing negative for BRCA1 and BRCA2.

      Ingham, S; Warwick, J; Buchan, I; Sahin, S; O'Hara, Catherine; Moran, Anthony; Howell, Anthony; Evans, D; Centre for Health Informatics, Institute of Population Health, The University of Manchester, Manchester, UK. (2013-06)
      Mutations in BRCA1/2 genes confer ovarian, alongside breast, cancer risk. We examined the risk of developing ovarian cancer in BRCA1/2-positive families and if this risk is extended to BRCA negative families.
    • Thumbnail

      AZD8186 study 1: phase I study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumour activity of AZD8186 in patients with advanced castration-resistant prostate cancer (CRPC), squamous non-small cell lung cancer, triple negative breast cancer and with PTEN-deficient/mutated or PIK3CB mutated/amplified malignancies, as monotherapy and in combination with vistusertib (AZD2014) or abiraterone acetate.

      Lillian, S; De Bono, J; Higano, C; Shapiro, G; Brugger, W; Mitchell, P; Colebrook, S; Klinowska, T; Barry, S; Dean, Emma J; et al. (2016-12)
    DSpace software (copyright © 2002 - 2025)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.