Retrospective study of dasatinib for recurrent glioblastoma after bevacizumab failure.

摘要: There is no effective treatment for recurrent glioblastoma (GBM) after bevacizumab failure. Putative mechanisms of resistance to include increased pericyte coverage, mediated partly by platelet-derived growth factor receptor (PDGFR) signaling, and an infiltrative tumor pattern potentially dependent on SRC. We explored the efficacy dasatinib, a SRC, BCR-ABL, c-KIT, EPHA2, PDGFRβ inhibitor, in patients with GBM Adult histologically confirmed who failed therapy were treated dasatinib 70–100 mg twice daily combination (n = 14), until progression or unacceptable toxicity. Fourteen treated. Median age was 55 years (range 32–66) median KPS 80 50–90). All (100%) had glioblastomas. The number prior regimens 4 from 2 6). Of thirteen evaluable patients, none complete partial response. Only one patient stable disease 8 week interval. progression-free survival (PFS) 28 days (95% confidence interval [CI] 26–35 days). Six month (PFS6) 0%. overall (OS) 78 CI 41–137 Treatment moderately well-tolerated, although sustained grade intracerebral hemorrhage. Dasatinib conjunction does not appear have activity recurrent, heavily pretreated GBM.