Pilot study of the combination of EGFR and mTOR inhibitors in recurrent malignant gliomas.
Malignant gliomas are frequently characterized by amplification of the epidermal growth factor receptor (EGFR) and loss of PTEN tumor suppressor gene. Twenty-eight heavily pretreated patients with recurrent malignant gliomas were administered EGFR inhibitors (gefitinib or erlotinib) in combination with the mTOR (mammalian target of rapamycin) inhibitor sirolimus. The regimens were reasonably well tolerated. Nineteen percent of patients experienced a partial response and 50% had stable disease. Six-month progression-free survival for glioblastoma patients was 25%.
Doherty
L
L
Center for Neuro-Oncology, Dana Farber/Brigham and Women's Cancer Center, Boston, MA 02115, USA.
Gigas
D C
DC
Kesari
S
S
Drappatz
J
J
Kim
R
R
Zimmerman
J
J
Ostrowsky
L
L
Wen
P Y
PY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011494:Protein Kinases / Q000502:physiology*; D012008:Recurrence; D012189:Retrospective Studies; D058570:TOR Serine-Threonine Kinases
D004791:Enzyme Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases