The efficacy of small-molecule
kinase inhibitors has recently changed standard clinical practice for several solid
cancers.
Glioblastoma is a solid
cancer that universally recurs and unrelentingly results in death despite maximal surgery and
radiotherapy with concomitant and adjuvant
temozolomide. Several clinical studies using
kinase inhibitors in
glioblastoma have been reported. The present study systematically reviews the efficacy, toxicity, and tissue analysis of small-molecule
kinase inhibitors in adult patients with
glioblastoma as reported in published clinical studies and determines which
kinases have been targeted by the inhibitors used in these studies. Publications were retrieved using a MEDLINE search and by screening meeting abstracts. A total of 60 studies qualified for inclusion, of which 25 were original reports. A total of 2385
glioblastoma patients receiving
kinase inhibitors could be evaluated. The study designs included 2 phase III studies and 37 phase II studies. Extracted data included radiological response, progression-free survival, overall survival, toxicity, and
biomarker analysis. The main findings were that (i) efficacy of small-molecule
kinase inhibitors in clinical studies with
glioblastoma patients does not yet warrant a change in standard clinical practice and (ii) 6 main
kinase targets for inhibitors have been evaluated in these studies: EGFR, mTOR, KDR, FLT1, PKCbeta, and PDGFR.