title: Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure.
abstract: There is no effective treatment for recurrent glioblastoma (GBM) after bevacizumab failure. Putative mechanisms of resistance to bevacizumab include increased pericyte coverage, mediated partly by platelet-derived growth factor receptor (PDGFR) signaling, and an infiltrative tumor growth pattern potentially dependent on SRC. We explored the efficacy of dasatinib, a SRC, BCR-ABL, c-KIT, EPHA2, and PDGFRβ inhibitor, in patients with recurrent GBM after bevacizumab failure. Adult patients with histologically confirmed GBM who failed bevacizumab therapy were treated with dasatinib 70-100 mg twice daily in combination with bevacizumab (n = 14), until tumor progression or unacceptable toxicity. Fourteen patients were treated. Median age was 55 years (range 32-66) and median KPS was 80 (range 50-90). All patients (100%) had glioblastomas. The median number of prior regimens was 4 (range from 2 to 6). Of the thirteen evaluable patients, none had a complete or partial response. Only one patient had stable disease after an 8 week interval. Median progression-free survival (PFS) was 28 days (95% confidence interval [CI] 26-35 days). Six month progression-free survival (PFS6) was 0%. Median overall survival (OS) was 78 days (95% CI 41-137 days). Treatment was moderately well-tolerated, although one patient sustained a grade 4 intracerebral hemorrhage. Dasatinib in conjunction with bevacizumab does not appear to have activity in patients with recurrent, heavily pretreated GBM.
authors.affiliation: Center for Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, 44 Binney Street, SW 430, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Lu-Emerson
authors.forename: A D
authors.initials: AD
authors.lastname: Norden
authors.forename: J
authors.initials: J
authors.lastname: Drappatz
authors.forename: E C
authors.initials: EC
authors.lastname: Quant
authors.forename: R
authors.initials: R
authors.lastname: Beroukhim
authors.forename: A S
authors.initials: AS
authors.lastname: Ciampa
authors.forename: L M
authors.initials: LM
authors.lastname: Doherty
authors.forename: D C
authors.initials: DC
authors.lastname: Lafrankie
authors.forename: S
authors.initials: S
authors.lastname: Ruland
authors.forename: P Y
authors.initials: PY
authors.lastname: Wen
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D000069439:Dasatinib; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D013844:Thiazoles; D000068258:Bevacizumab; D000069439:Dasatinib