Regorafenib for treatment of advanced gastrointestinal stromal Tumors

Lindsay C. Overton, Michael Heinrich

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    Introduction: Gastrointestinal stromal tumors (GISTs) are abdominal sarcomas which are extremely refractory to chemotherapy treatment. The treatment of GISTs has been revolutionized by use of KIT/platelet-derived growth factor receptor-α (PDGFRA) kinase inhibitors. Unfortunately, most tumors develop resistance to front-line (imatinib) or second-line (sunitinib) therapy. Regorafenib, a KIT/PDGFRA/vascular endothelial growth factor receptor (VEGFR) oral kinase inhibitor, has been shown to improve progression-free survival in the third- or fourth-line setting. Areas covered: This review covers the preclinical and clinical studies of regorafenib for treatment of GIST. A literature search on regorafenib was carried out using the PubMed database up to October 2013. Expert opinion: Currently, imatinib and sunitinib represent the only proven first- and second-line therapies, respectively, for advanced GISTs. Based on the results of a Phase III study, regorafenib is now established as the only proven third-line therapy. Regorafenib activity in this setting is believed to be due to its activity against oncogenic forms of KIT/PDGFRA. Although side effects are common with this agent, they can be effectively managed with a combination of supportive care, dose interruptions/reductions. The toxicity profile is similar to other oral kinase inhibitors with anti-VEGFR activity. Regorafenib is mainly metabolized by CYP3A4, and concomitant use of strong inducers/inhibitors of this enzyme should be avoided.

    Original languageEnglish (US)
    Pages (from-to)549-558
    Number of pages10
    JournalExpert Opinion on Pharmacotherapy
    Volume15
    Issue number4
    DOIs
    StatePublished - Mar 2014

    Fingerprint

    Gastrointestinal Stromal Tumors
    Vascular Endothelial Growth Factor Receptor
    Phosphotransferases
    Therapeutics
    Platelet-Derived Growth Factor Receptors
    Cytochrome P-450 CYP3A
    Expert Testimony
    Enzyme Inhibitors
    PubMed
    Sarcoma
    Disease-Free Survival
    regorafenib
    Databases
    Drug Therapy
    Neoplasms

    Keywords

    • Gastrointestinal stromal tumor
    • Kinase inhibitors
    • KIT
    • Platelet-derived growth factor receptor α
    • Sarcoma
    • Vascular endothelial growth factor receptor

    ASJC Scopus subject areas

    • Pharmacology (medical)
    • Pharmacology

    Cite this

    Regorafenib for treatment of advanced gastrointestinal stromal Tumors. / Overton, Lindsay C.; Heinrich, Michael.

    In: Expert Opinion on Pharmacotherapy, Vol. 15, No. 4, 03.2014, p. 549-558.

    Research output: Contribution to journalArticle

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